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Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic., Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors., Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022., Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation., Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64)., Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Background: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma., Methods: Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety., Results: Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3 + infiltrates. Surprisingly, the baseline cell density of CD3 + CD8 - T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179)., Conclusions: These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment., Trial Registration Number: NCT02565992., (© 2022. The Author(s).)

Small non-coding RNAs are potential diagnostic biomarkers for lung cancer. Mitochondria-derived small RNA (mtRNA) is a novel regulatory small non-coding RNA that only recently has been identified and cataloged. Currently, there are no reports of studies of mtRNA in human lung cancer. Currently, normalization methods are unstable, and they often fail to identify differentially expressed small non-coding RNAs (sncRNAs). In order to identify reliable biomarkers for lung cancer screening, we used a ratio-based method using mtRNAs newly discovered in human peripheral blood mononuclear cells. In the discovery cohort (AUC = 0.981) and independent validation cohort (AUC = 0.916) the prediction model of eight mtRNA ratios distinguished lung cancer patients from controls. The prediction model will provide reliable biomarkers that will allow blood-based screening to become more feasible and will help make lung cancer diagnosis more accurate in clinical practice., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Many patients with metastatic breast cancer develop liver metastases. A rare complication of this is hepatopulmonary syndrome (HPS), which is associated with exertional dyspnea and intrapulmonary shunting. We present a patient who presented with HPS as a consequence of liver metastases and subsequently treated with chemotherapy leading to resolution of her symptoms., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)

Treatment of metastatic melanoma has changed dramatically in the past 5 years with the approval of six new agents (vemurafenib, dabrafenib, trametinib, ipilimumab, pembrolizumab, and nivolumab) by the US Food and Drug Administration (FDA). This review will compare the immunotherapies recently approved by the FDA (ipilimumab, nivolumab and pembrolizumab) with the long-approved immunotherapy, interleukin-2. Additional consideration will be given to the evolving landscape, including the opportunities for combination regimens. Immunotherapies have distinct mechanisms of action and unique response kinetics that differ from conventional cytotoxic and targeted therapies, and have a range of adverse events that can be safely managed by experienced health-care providers. Data suggest immunotherapies can result in long-term survival in a proportion of patients. This dynamic and evolving field of immunotherapy for melanoma will continue to offer challenges in terms of optimal patient management for the foreseeable future.

Background/aim: Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique., Patients and Methods: From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported., Results: A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively., Conclusion: SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Competing Interests: Conflicts of Interest The authors do not report any disclosures or conflicts of interest related to this manuscript.

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71-83). The median survival was 18 months (IQR: 10-31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Purpose: We report treatments and outcomes in a contemporary patient population with HER2-positive metastatic breast cancer (MBC) by hormone receptor (HR) status from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs)., Experimental Design: SystHERs (NCT01615068) was an observational, prospective registry study of U.S.-based patients with newly diagnosed HER2-positive MBC. Endpoints included treatment patterns and clinical outcomes., Results: Of 977 eligible patients (enrolled from 2012 to 2016), 70.1% ( n = 685) had HR-positive and 29.9% ( n = 292) had HR-negative disease. Overall, 59.1% (405/685) of patients with HR-positive disease received any first-line endocrine therapy (with or without HER2-targeted therapy or chemotherapy); 34.9% (239/685) received HER2-targeted therapy + chemotherapy + sequential endocrine therapy. Patients with HR-positive versus HR-negative disease had longer median overall survival (OS; 53.0 vs 43.4 months; hazard ratio, 0.70; 95% confidence interval, 0.56-0.87). Compared with patients with high HR-positive staining (10%-100%, n = 550), those with low HR-positive staining (1%-9%, n = 60) received endocrine therapy less commonly (64.2% vs 33.3%) and had shorter median OS (53.8 vs 40.1 months). Similar median OS (43.4 vs 40.1 months) was observed in patients with HR-negative versus low HR-positive tumors (1%-9%)., Conclusions: Despite evidence that first-line HER2-targeted therapy, chemotherapy, and sequential endocrine therapy improves survival in patients with HR-positive, HER2-positive disease, only 34.9% of patients in this real-world setting received such treatment. Patients with low tumor HR positivity (1%-9%) had lower endocrine therapy use and worse survival than those with high tumor HR positivity (10%-100%)., (©2020 American Association for Cancer Research.)

Given the high prevalence (30-35%) of psychosocial and psychiatric morbidity amongst cancer patients in any phase of the disease trajectory, screening for emotional problems and disorders has become mandatory in oncology. As a process, screening begins at the entry to the cancer care system and continues at clinically meaningful times, periodically during active cancer care, or when clinically indicated. The goal is to facilitate proper referral to psychosocial oncology specialists for more specific assessment and care, as well as treatment and evaluation of the response, according to the implementation of distress management guidelines. In this editorial, we will provide a non-exhaustive overview of relevant protocols, with particular reference to the National Comprehensive Cancer Network (NCCN) Distress Management in Oncology Guidelines, and review the challenges and the problems in implementing screening, and the assessment and management of psychosocial and psychiatric problems in cancer centres and community care.

Interleukin-17 (IL-17), a proinflammatory cytokine, mainly produced by Th17 cells, participates in both innate and adaptive immune responses and is involved in various diseases, including infectious diseases, autoimmune disorders and cancer. Emerging evidence indicates that IL-17 not only has an oncogenic role in tumorigenesis by regulating tumor angiogenesis and enhancing tumor immune evasion but also exerts anti-tumor functions by enhancing natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) activation and through the recruitment of neutrophils, NK cells and CD4 + and CD8 + T cells to tumor tissue. In this review, we provide an overview on the basic biology of IL-17 and recent findings regarding its enigmatic double-edged features in tumorigenesis, with special attention to the roles of IL-17 produced by tumor cells interacting with other factors in the tumor microenvironment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Surgical site infection (SSI) remains one of the most important causes of healthcare-associated infections, accounting for ~17 % of all hospital-acquired infections. Although short-term perioperative treatment with high fraction of inspired oxygen (FiO2) has shown clinical benefits in reducing SSI in colorectal resection surgeries, the true clinical benefits of FiO2 therapy in reducing SSI remain unclear because randomized controlled trials on this topic have yielded disparate results and inconsistent conclusions. To date, no animal study has been conducted to determine the efficacy of short-term perioperative treatments with high (FiO2>60 %) versus low (FiO2<40 %) oxygen in reducing SSI. In this report, we designed a rat model for muscle surgery to compare the effectiveness of short-term perioperative treatments with high (FiO2=80 %) versus a standard low (FiO2=30 %) oxygen in reducing SSI with Pseudomonas aeruginosa - one of the most prevalent Gram-negative pathogens, responsible for nosocomial SSIs. Our data demonstrate that 5 h perioperative treatment with 80 % FiO2 is significantly more effective in reducing SSI with P. aeruginosa compared to 30 % FiO2 treatment. We further show that whilst 80 % FiO2 treatment does not affect neutrophil infiltration into P. aeruginosa-infected muscles, neutrophils in the 80 % FiO2-treated and infected animal group are significantly more activated than neutrophils in the 30 % FiO2-treated and infected animal group, suggesting that high oxygen perioperative treatment reduces SSI with P. aeruginosa by enhancing neutrophil activation in infected wounds.

Background: Snail is a typical transcription factor that could induce epithelial-mesenchymal transition (EMT) and cancer progression. There are some related reports about the clinical significance of snail protein expression in gastric cancer. However, the published results were not completely consistent. This study was aimed to investigate snail expression and clinical significance in gastric cancer., Results: A systematic review of PubMed, CNKI, Weipu, and Wanfang database before March 2015 was conducted. We established an inclusion criterion according to subjects, method of detection, and results evaluation of snail protein. Meta-analysis was conducted using RevMan4.2 software. And merged odds ratio (OR) and 95 % CI (95 % confidence interval) were calculated. Also, forest plots and funnel plot were used to assess the potential of publication bias. A total of 10 studies were recruited. The meta-analysis was conducted to evaluate the positive rate of snail protein expression. OR and 95 % CI for different groups were listed below: (1) gastric cancer and para-carcinoma tissue [OR = 6.15, 95 % CI (4.70, 8.05)]; (2) gastric cancer and normal gastric tissue [OR = 17.00, 95 % CI (10.08, 28.67)]; (3) non-lymph node metastasis and lymph node metastasis [OR = 0.40, 95 % CI (0.18, 0.93)]; (4) poor differentiated cancer, highly differentiated cancer, and moderate cancer [OR = 3.34, 95 % CI (2.22, 5.03)]; (5) clinical stage TI + TII and stage TIII + TIV [OR = 0.38, 95 % CI (0.23, 0.60)]; (6) superficial muscularis and deep muscularis [OR = 0.18, 95 % CI (0.11, 0.31)]., Conclusions: Our results indicated that the increase of snail protein expression may play an important role in the carcinogenesis, progression, and metastasis of gastric cancer. And this result might provide instruction for the diagnosis, therapy, and prognosis of gastric cancer.

Stable blood based miRNA species have allowed for the differentiation of patients with various types of cancer. Therefore, specific blood-based miRNA might be considered as a methodology which could be informative of the presence of cancer potentially from multiple distinct organ sites. Recently, miR-21 has been identified as an "oncomir" in various tumors while miR-152 as a tumor suppressor. In this study, we investigated whether circulating miR-21 and miR-152 can be used for early detection of lung cancer (LuCa), colorectal carcinoma (CRC), breast cancer (BrCa) and prostate cancer (PCa), with distinguishing cancer from various benign lesions on these organ sites. We measured the two miRNA levels by using real-time RT-PCR in plasma samples from a total of 204 cancer patients, 159 various benign lesions, and 228 normal subjects. We observed significantly elevated expression of miR-21 and miR-152 in LuCa, CRC, and BrCa when compared with normal controls. We also found upregulation of plasma miR-21 and miR-152 levels in patients with benign lesions of lung and breast, as compared to normal controls, respectively. No significant expression variation of the two miRNAs was observed in PCa or prostatic benign lesions as compared to healthy controls. Receiver operating characteristic (ROC) analyses revealed that miR-21 and/or miR-152 can discriminate LuCa, CRC and BrCa from normal controls. Our results suggest that plasma miR-21 and miR-152 may serve as non-specific noninvasive biomarkers for early screening of LuCa, CRC, and BrCa, but not PCa.

Background: Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model., Results: We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models., Conclusions: We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

The IKZF2 rs12619285 polymorphism is associated with the eosinophil count, which has multidimensional functions in the pathogenesis of coronary heart disease (CHD). The aim of the present study was to investigate the contribution of the IKZF2 rs12619285 polymorphism to the risk of CHD in a Han Chinese population. In total, 721 CHD cases and 631 non-CHD controls were recruited for an association study of the IKZF2 rs12619285 polymorphism. Genotyping was performed using the melting temperature-shift polymerase chain reaction method. No statistically significant association was observed between the IKZF2 rs12619285 polymorphism and CHD (odds ratio, 1.139, 95% confidence interval, 0.927-1.334; P=0.17). In addition, subgroup analyses by gender or age were unable to identify any association between IKZF2 rs12619285 and CHD (P>0.05), and there was no significant correlation between IKZF2 rs12619285 and the severity of CHD (P>0.05). The power of the case-control study was determined to be 63.3%. In addition, the G allele frequency was calculated as 63.6% in the Han Chinese population, which was similar to the 59.3% recorded for the HapMap Chinese population of Han Chinese individuals living in Beijing, compared with 24.3% in European descendents (HapMap-CEU). Therefore, the results indicated that the IKZF2 rs12619285 polymorphism was not associated with CHD in a Han Chinese population. The discrepancy in the association between rs12619285 and CHD may be due to the ethnic differences between Han Chinese and European populations.

In patients with malignancy, the major barrier to achieving complete response is emergence of resistance to current chemotherapeutic agents. One of the major mechanisms by which tumour cells become resistant to therapies is by altering cellular drug targets through mutations and/or deletions. Resistance by this mechanism is achieved more easily if the drug has limited cellular targets and/or processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) targets six proteins that are required for cancer cell survival and proliferation, it is highly unlikely for cancer cells to develop resistance to this toxin. We assessed ExoT's cytotoxicity against multiple invasive and highly resistant tumour cell lines in order to evaluate its potential as a chemotherapeutic agent. Our data demonstrated that ExoT induced potent cytotoxicity in all tumour cell lines that we examined. Collectively, our data highlighted the potential of ExoT as a possible chemotherapeutic candidate for the treatment of cancer., (© 2015 The Authors.)

Decline in CD4 T cell immune responses is associated with aging. Although a number of immunological defects have been identified in elderly mice (>18 months old), a key early-onset immune defect at middle age could be a driver or contributor to defective CD4 T cell responses. Our studies demonstrate that age-related alterations in DC subsets within the priming environment of middle-aged mice (12 months old) correlate with and can directly contribute to decreases in antigen-specific CD4 T cell Th1 differentiation, which measured by T-bet and IFN-γ expression, was decreased significantly in T cells following VSV infection or s.c. immunization with a protein antigen in the context of immune stimulation via OX40. The deficient Th1 phenotype, observed following protein antigen challenge, was found to be the result of an age-related decrease in an inflammatory DC subset (CD11b+ Gr-1/Ly6C+) in the dLN that corresponded with T cell dysfunction. In the virus model, we observed significant changes in two DC subsets: mDCs and pDCs. Thus, different, early age-related changes in the DC profile in the priming environment can significantly contribute to impaired Th1 differentiation, depending on the type of immunological challenge., (© 2014 Society for Leukocyte Biology.)

Background: High throughput transcriptomics profiles such as those generated using microarrays have been useful in identifying biomarkers for different classification and toxicity prediction purposes. Here, we investigated the use of microarrays to predict chemical toxicants and their possible mechanisms of action., Results: In this study, in vitro cultures of primary rat hepatocytes were exposed to 105 chemicals and vehicle controls, representing 14 compound classes. We comprehensively compared various normalization of gene expression profiles, feature selection and classification algorithms for the classification of these 105 chemicals into14 compound classes. We found that normalization had little effect on the averaged classification accuracy. Two support vector machine (SVM) methods, LibSVM and sequential minimal optimization, had better classification performance than other methods. SVM recursive feature selection (SVM-RFE) had the highest overfitting rate when an independent dataset was used for a prediction. Therefore, we developed a new feature selection algorithm called gradient method that had a relatively high training classification as well as prediction accuracy with the lowest overfitting rate of the methods tested. Analysis of biomarkers that distinguished the 14 classes of compounds identified a group of genes principally involved in cell cycle function that were significantly downregulated by metal and inflammatory compounds, but were induced by anti-microbial, cancer related drugs, pesticides, and PXR mediators., Conclusions: Our results indicate that using microarrays and a supervised machine learning approach to predict chemical toxicants, their potential toxicity and mechanisms of action is practical and efficient. Choosing the right feature and classification algorithms for this multiple category classification and prediction is critical.

Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older), and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif) ligand 2 (CCL2) expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds.

Background: Oncolytic viruses represent a novel form of cancer immunotherapy. Vaccinia viruses encoding human T cell co-stimulatory molecules have demonstrated clinical activity in phase I clinical trials in patients with advanced melanoma. However, predictive biomarkers of therapeutic response have not yet been identified., Methods: A customized microarray was performed to identify changes in peripheral blood mononuclear cell (PBMC) gene expression upon exposure to recombinant oncolytic vaccinia viruses. Up-regulated and down-regulated genes were identified and selected for further analysis using PBMC samples from normal donors and oncolytic virus-treated patients before and after viral injection. Quantitative PCR and flow cytometry of defined T cell subsets was performed to evaluate expression patterns and clinical correlations., Results: The microarray identified 301 genes that were up-regulated and 960 genes that were down-regulated in T cells after exposure to oncolytic vaccinia virus. The B7.1 gene was highly up-regulated and the immunoglobulin-like transcript 2 (ILT2) gene was highly down-regulated by vaccinia-B7.1, which was consistent with the known inverse regulation of these two genes. We observed an inverse association between ILT2 expression in the tumor microenvironment and clinical response and further identified ILT2 as a marker of regulatory CD4+ and suppressor CD8+ T cell responses and whose down-regulation was predictive of therapeutic responses in patients treated with oncolytic virus immunotherapy., Conclusions: ILT2 is a new putative biomarker of T cell and clinical response in patients treated with oncolytic vaccinia virus immunotherapy. Further confirmation of ILT2 as a biomarker requires prospective validation in a larger series of clinical trials.

Achieving improvements in survival and reducing relapse remains a challenge in acute myelogenous leukemia (AML) patients. This study evaluated the in vitro efficacy of the active form of novel agent sapacitabine, CNDAC, compared to current chemotherapeutic drugs Ara-C and mitoxantrone using two AML cell lines, HL-60 (promyelocytic) and THP-1 (monocytic), as well as bone marrow (BM) and peripheral blood (PB) cells collected from AML patients. Cell lines were exposed to compound for 3-6 days and primary cells for 4 days. The viability of primary cells was additionally evaluated 3, 7, and 31 days after removal of tested compound to determine the durability of the response. Our studies indicate that CNDAC and mitoxantrone have a greater impact on viability than ara-C in primary AML cells and AML cell lines. CNDAC is more effective at reducing viability and inducing apoptosis than ara-C at equivalent concentrations in the THP-1 cell line, which is defined as displaying resistance to ara-C. As sapacitabine has shown in vivo activity at clinically achievable doses, future studies are warranted to assess the potential for combining it with ara-C and/or mitoxantrone, with an emphasis on cells and patients insensitive to ara-C treatment.