Epigenetic modulation in sensitizing metastatic sarcomas to therapies and overcoming resistance

Sarcomas are a class of rare malignancies of mesenchymal origin with a heterogeneous histological spectrum. They are classically associated with poor outcomes, especially once metastasized. A path to improving clinical outcomes may be made through modifying the epigenome, where a variety of sarcomas demonstrate changes that contribute to their oncogenic phenotypes. This Perspective article identifies and describes changes in the sarcoma genome, while discussing specific epigenetic changes and their effect on clinical outcomes. Clinical attempts at modulating epigenetics in sarcoma are reviewed, as well as potential implications of these studies. Epigenetic targets to reverse and delay chemotherapy resistance are discussed. Future directions with primary next steps are proposed to invigorate the current understanding of epigenetic biomarkers to enact targeted therapies to epigenetic phenotypes of sarcoma subtypes. Modifications to prior studies, as well as proposed clinical steps, are also addressed.

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Alanine Aminotransferase Predicts Outcomes in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage

Current Neurovascular Research ◽

10.2174/1567202616666190130094631 ◽

2019 ◽

Vol 16 (1) ◽

pp. 89-95

Author(s):

Jianfeng Zheng ◽

Rui Xu ◽

Zongduo Guo ◽

Xiaochuan Sun

Keyword(s):

Subarachnoid Hemorrhage ◽

Elderly Patients ◽

Clinical Outcomes ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Laboratory Data ◽

Cardiac Complications ◽

World Population ◽

Systemic Complications ◽

Poor Outcome ◽

Poor Outcomes

Objective: With the aging of the world population, the number of elderly patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is gradually growing. We aim to investigate the potential association between plasma ALT level and clinical complications of elderly aSAH patients, and explore its predictive value for clinical outcomes of elderly aSAH patients. Methods: Between January 2013 and March 2018, 152 elderly aSAH patients were analyzed in this study. Clinical information, imaging findings and laboratory data were reviewed. According to the Glasgow Outcome Scale (GOS), clinical outcomes at 3 months were classified into favorable outcomes (GOS 4-5) and poor outcomes (GOS 1-3). Logistic regression analysis was used to assess the indicators associated with poor outcomes, and receiver curves (ROC) and corresponding area under the curve (AUC) were used to detect the accuracy of the indicator. Results: A total of 48 (31.6 %) elderly patients with aSAH had poor outcome at 3 months. In addition to ICH, IVH, Hunt-Hess 4 or 5 Grade and Modified Fisher 3 or 4 Grade, plasma ALT level was also strongly associated with poor outcome of elderly aSAH patients. After adjusting for other covariates, plasma ALT level remained independently associated with pulmonary infection (OR 1.05; 95% CI 1.00–1.09; P = 0.018), cardiac complications (OR 1.05; 95% CI 1.01–1.08; P = 0.014) and urinary infection (OR 1.04; 95% CI 1.00–1.08; P = 0.032). Besides, plasma ALT level had a predictive ability in the occurrence of systemic complications (AUC 0.676; 95% CI: 0.586– 0.766; P<0.001) and poor outcome (AUC 0.689; 95% CI: 0.605–0.773; P<0.001) in elderly aSAH patients. Conclusion: Plasma ALT level of elderly patients with aSAH was significantly associated with systemic complications, and had additional clinical value in predicting outcomes. Given that plasma ALT levels on admission could help to identify high-risk elderly patients with aSAH, these findings are of clinical relevance.

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Genetics of canine diabetes mellitus part 2: Current understanding and future directions

The Veterinary Journal ◽

10.1016/j.tvjl.2021.105612 ◽

2021 ◽

Vol 270 ◽

pp. 105612

Author(s):

Alice L. Denyer ◽

Brian Catchpole ◽

Lucy J. Davison

Keyword(s):

Diabetes Mellitus ◽

Current Understanding ◽

Future Directions ◽

Canine Diabetes Mellitus

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Prolonged Survival in Patients with Metastatic HER2-Positive Inflammatory Breast Cancer: A Case Report and Review of the Literature

Case Reports in Oncology ◽

10.1159/000516760 ◽

2021 ◽

pp. 1071-1079

Author(s):

Jennifer Y. Ge ◽

Beth Overmoyer

Keyword(s):

Breast Cancer ◽

Case Report ◽

Inflammatory Breast Cancer ◽

Targeted Therapies ◽

De Novo ◽

Review Of The Literature ◽

Her2 Positive ◽

Rare Type ◽

Favorable Prognosis ◽

Poor Outcomes

Inflammatory breast cancer (IBC) is a rare type of breast cancer that is associated with poor outcomes compared with non-IBC. Overexpression of HER2 is enriched in IBC, and those with HER2-positive disease have a relatively favorable prognosis, with improved survival over the last two decades driven by the advent of novel targeted therapies. Here, we present two patients who have survived for over 10 years after being diagnosed with de novo metastatic HER2-positive IBC. We review the data for the treatments available for metastatic HER2-positive IBC and the evolving treatment recommendations for this disease.

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Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC

International Journal of Cancer ◽

10.1002/ijc.31895 ◽

2018 ◽

Vol 144 (11) ◽

pp. 2677-2682 ◽

Cited By ~ 11

Author(s):

Jinguang Wang ◽

Xingya Li ◽

Xingyang Xue ◽

Qiuxiang Ou ◽

Xue Wu ◽

...

Keyword(s):

Clinical Outcomes ◽

Targeted Therapies ◽

Kinase Domain ◽

Domain Duplication ◽

Egfr Kinase

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The association between neutrophil–lymphocyte ratio and poor outcomes following infant cardiac surgery

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02345-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Peng Gao ◽

Jinping Liu ◽

Xu Wang ◽

Peiyao Zhang ◽

Yu Jin ◽

...

Keyword(s):

Mechanical Ventilation ◽

Logistic Regression ◽

Cardiac Surgery ◽

Hospital Stay ◽

Clinical Outcomes ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Time Length ◽

Mechanical Ventilation Time ◽

Poor Outcomes

Abstract Background Neutrophil–lymphocyte ratio (NLR) is a valuable indicator for evaluating inflammation and adverse outcomes after cardiac surgery. The objective of this study was to evaluate the association of perioperative NLR with clinical outcomes in infants undergoing congenital heart surgery with cardiopulmonary bypass. Methods We performed a retrospective review of 424 consecutive infants (≤ 1 year) undergoing cardiac surgery between January 2019 and September 2019. Neonates (≤ 28 days) and patients with incomplete NLR data were excluded. The study endpoint was a composite of poor outcomes after surgery. We assess the correlation between perioperative NLR and clinical outcomes. A receiver operating characteristic curve and multivariable logistic regression were applied to identify the prognosis performance of postoperative NLR for poor outcomes. Results A total of 68 (16%) infants experienced at least one of the poor outcomes. Postoperative NLR on the third day after the surgery showed the best prognostic significance (AUC = 0.763, 95%CI 0.700–0.826) among perioperative period, with a cut-off value of 2.05. Postoperative NLR was also strongly correlated with mechanical ventilation time, length of ICU and hospital stay (p < 0.001). Multivariable logistic regression revealed that elevated postoperative NLR (OR 3.722, 95%CI 1.895–7.309, p < 0.001) was an independent risk factor for poor outcomes in infants after cardiac surgery. Conclusions Postoperative NLR was correlated with increased mechanical ventilation time, length of ICU and hospital stay. Elevated postoperative NLR was an independent predictor for poor outcomes after cardiac surgery in infants.

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Glial Cells, Maladaptive Plasticity and Neurodegeneration: Mechanisms, Targeted Therapies and Future Directions

10.3389/978-2-88966-937-0 ◽

2021 ◽

Keyword(s):

Glial Cells ◽

Targeted Therapies ◽

Future Directions ◽

Maladaptive Plasticity

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Epigenetics in Psychiatry

Psychiatric Genetics ◽

10.1093/med/9780190221973.003.0011 ◽

2018 ◽

pp. 165-183

Author(s):

Subha Subramanian ◽

James B. Potash

Keyword(s):

Dna Methylation ◽

Human Brain ◽

Psychiatric Disorders ◽

Drugs Of Abuse ◽

Future Directions ◽

Peripheral Tissues ◽

Risk Genes ◽

Epigenetic Biomarkers ◽

Ongoing Work ◽

The Impact

Epigenetic modifications such as DNA methylation (DNAm), histone acetylation and methylation, and those directed by small RNAs, are widely studied in psychiatry and may play a role in the etiology and pathophysiology of psychiatric disorders. This chapter provides a brief overview of the mechanisms regulating these epigenetic marks and the challenges in obtaining biologically meaningful epigenetic data, given the inaccessibility of the living human brain. Significant results to date from studies on the epigenetics of psychiatric disorders are presented, including the impact of stress on DNAm in psychiatric risk genes such as FKBP5, and the impact of drugs of abuse and of psychiatric medications on histone modifications. Future directions are discussed, including the study of newly discovered aspects of DNAm: 5-hydroxymethylcytosine and non-CpG methylation. Ongoing work aims to uncover neurobiological mechanisms of illness and to find epigenetic biomarkers in peripheral tissues that inform diagnosis, prognosis, and therapeutic response.

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Recent advances in understanding necrotizing enterocolitis

F1000Research ◽

10.12688/f1000research.17228.1 ◽

2019 ◽

Vol 8 ◽

pp. 107 ◽

Cited By ~ 8

Author(s):

Mashriq Alganabi ◽

Carol Lee ◽

Edoardo Bindi ◽

Bo Li ◽

Agostino Pierro

Keyword(s):

Risk Factors ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Advanced Disease ◽

Current Understanding ◽

Disease Development ◽

Current Management ◽

Future Directions ◽

Ongoing Research ◽

Factors Associated

Necrotizing enterocolitis is a devastating intestinal disease affecting preterm infants. In spite of ongoing research and advancement in neonatal care, mortality remains high, especially in infants with advanced disease. The mechanism of disease development, the progression of intestinal injury, and management remain areas of ongoing research and controversy. In this review, we examine our current understanding of the disease, its epidemiology, the risk factors associated with the development of the disease, and its pathophysiology. We also describe current management and new emerging research highlighting potential future directions.

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Intracerebral hemorrhage location and outcome among INTERACT2 participants

Neurology ◽

10.1212/wnl.0000000000003771 ◽

2017 ◽

Vol 88 (15) ◽

pp. 1408-1414 ◽

Cited By ~ 39

Author(s):

Candice Delcourt ◽

Shoichiro Sato ◽

Shihong Zhang ◽

Else Charlotte Sandset ◽

Danni Zheng ◽

...

Keyword(s):

Quality Of Life ◽

Intracerebral Hemorrhage ◽

Clinical Outcomes ◽

Utility Score ◽

Blood Pressure Reduction ◽

Internal Capsule ◽

Posterior Limb ◽

Quality Of Life Scale ◽

Poor Outcomes

Objective:To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).Methods:Associations between ICH sites and poor outcomes (death [6] or major disability [3–5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models.Results:Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score (≤0.7 [median]; OR 1.87, 2.14, and 2.81, respectively). Posterior limb of internal capsule involvement was strongly associated with low scores across all health-related quality of life domains. ICH encompassing the thalamus and posterior limb of internal capsule were associated with death or major disability, major disability, and poor EQ-5D utility score (OR 1.72, 2.26, and 1.71, respectively).Conclusion:Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule.ClinicalTrials.gov registration:NCT00716079.

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