scholarly journals COVID-19 Pandemic: Insights into Molecular Mechanisms Leading to Sex-based Differences in Patient Outcomes

2021 ◽  
pp. 1-38
Author(s):  
Ashutosh Kumar ◽  
Ravi K. Narayan ◽  
Maheswari Kulandhasamy ◽  
Pranav Prasoon ◽  
Chiman Kumari ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Molecular Mechanisms

scholarly journals Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10800
Author(s):  
Shubhangi Gavali ◽  
Jianing Liu ◽  
Xinyi Li ◽  
Magdalena Paolino
Keyword(s):  
T Cell ◽  
Patient Outcomes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Patient Treatment ◽  
Functional Roles ◽  
Protein Ubiquitination ◽  
Fine Tune

The advent of T-cell-based immunotherapy has remarkably transformed cancer patient treatment. Despite their success, the currently approved immunotherapeutic protocols still encounter limitations, cause toxicity, and give disparate patient outcomes. Thus, a deeper understanding of the molecular mechanisms of T-cell activation and inhibition is much needed to rationally expand targets and possibilities to improve immunotherapies. Protein ubiquitination downstream of immune signaling pathways is essential to fine-tune virtually all immune responses, in particular, the positive and negative regulation of T-cell activation. Numerous studies have demonstrated that deregulation of ubiquitin-dependent pathways can significantly alter T-cell activation and enhance antitumor responses. Consequently, researchers in academia and industry are actively developing technologies to selectively exploit ubiquitin-related enzymes for cancer therapeutics. In this review, we discuss the molecular and functional roles of ubiquitination in key T-cell activation and checkpoint inhibitory pathways to highlight the vast possibilities that targeting ubiquitination offers for advancing T-cell-based immunotherapies.

scholarly journals Modeling the developmental origins of pediatric cancer to improve patient outcomes

2021 ◽  
Vol 14 (2) ◽  
Author(s):  
James F. Amatruda
Keyword(s):  
Patient Outcomes ◽  
Pediatric Cancer ◽  
Molecular Mechanisms ◽  
Cellular Transformation ◽  
Genetic Changes ◽  
Current Therapies ◽  
Physician Scientist ◽  
Improve Patient ◽  
Generation Sequencing

ABSTRACT In the treatment of children and adolescents with cancer, multimodal approaches combining surgery, chemotherapy and radiation can cure most patients, but may cause lifelong health problems in survivors. Current therapies only modestly reflect increased knowledge about the molecular mechanisms of these cancers. Advances in next-generation sequencing have provided unprecedented cataloging of genetic aberrations in tumors, but understanding how these genetic changes drive cellular transformation, and how they can be effectively targeted, will require multidisciplinary collaboration and preclinical models that are truly representative of the in vivo environment. Here, I discuss some of the key challenges in pediatric cancer from my perspective as a physician-scientist, and touch on some promising new approaches that have the potential to transform our understanding of these diseases.

scholarly journals Insights into the pathogenesis of macrodactyly

2018 ◽  
Vol 44 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Marybeth Ezaki
Keyword(s):  
Environmental Factors ◽  
Patient Outcomes ◽  
Molecular Mechanisms ◽  
Mirror Image ◽  
Epigenetic Factors ◽  
Clinical Challenge ◽  
Size Asymmetry

Mirror-image symmetry in limbs is normal in the vertebrate phenotype. Genetic and epigenetic factors regulate the differentiation, patterning, and development of the embryo and foetus. Growth after birth is influenced by hormonal and environmental factors such as nutrition. Limb size asymmetry in a child should trigger a search for associated pathology that may include neoplastic conditions, sequelae of injury, vascular, and neurogenic factors. Macrodactyly, part of the PIK3CA Related Overgrowth Spectrum, offers the physician a clinical challenge, while at the same time an opportunity to study morphology, histology, and more recently the molecular mechanisms from which the conditions arise. Collaboration between clinicians and basic scientists offers an exceptional opportunity for coordinated study and the potential for improved patient outcomes.

scholarly journals Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Lukas Käsmann ◽  
Alexander Dietrich ◽  
Claudia A. Staab-Weijnitz ◽  
Farkhad Manapov ◽  
Jürgen Behr ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Patient Outcomes ◽  
Lung Fibrosis ◽  
Major Part ◽  
Molecular Mechanisms ◽  
Limiting Factors ◽  
Incidence And Mortality ◽  
High Incidence ◽  
Radiation Induced

Abstract Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.

scholarly journals The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Aging: Implications in Obesity and Cardiovascular Disease

2018 ◽  
Vol 19 (7) ◽  
pp. 2139 ◽  
Author(s):  
David Bartlett ◽  
Richard Miller ◽  
Scott Thiesfeldt ◽  
Hari Lakhani ◽  
Joseph Shapiro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Patient Outcomes ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
General Decline ◽  
Pumping Function ◽  
Improve Patient

Aging has been associated with a series of pathophysiological processes causing general decline in the overall health of the afflicted population. The cumulative line of evidence suggests an important role of oxidative stress in the development and progression of the aging process and metabolic abnormalities, exacerbating adipocyte dysfunction, cardiovascular diseases, and associated complications at the same time. In recent years, robust have established the implication of Na/K-ATPase signaling in causing oxidative stress and alterations in cellular mechanisms, in addition to its distinct pumping function. Understanding the underlying molecular mechanisms and exploring the possible sources of pro-oxidants may allow for developing therapeutic targets in these processes and formulate novel intervention strategies for patients susceptible to aging and associated complications, such as obesity and cardiovascular disease. The attenuation of oxidative stress with targeted treatment options can improve patient outcomes and significantly reduce economic burden.

Molecular Mechanisms for Sex-based Differences in Patient Outcomes in COVID-19: A Systematic Review

2020 ◽  
Author(s):  
Ashutosh Kumar ◽  
Maheswari Kulandhasamy ◽  
Pranav Prasoon ◽  
Ravi K. Narayan ◽  
Chiman Kumari ◽  
...  
Keyword(s):  
Systematic Review ◽  
Patient Outcomes ◽  
Molecular Mechanisms

Molecular mechanisms of ischemic conditioning: translation into patient outcomes

2013 ◽  
Vol 9 (4) ◽  
pp. 549-568 ◽  
Author(s):  
Matthew J Brooks ◽  
David T Andrews
Keyword(s):  
Patient Outcomes ◽  
Molecular Mechanisms ◽  
Ischemic Conditioning

scholarly journals Phenotypes from cell-free DNA

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200119
Author(s):  
Alexis Zukowski ◽  
Satyanarayan Rao ◽  
Srinivas Ramachandran
Keyword(s):  
Patient Outcomes ◽  
Gold Standard ◽  
Molecular Mechanisms ◽  
Underlying Disease ◽  
Clinical Practices ◽  
Cell Free Dna ◽  
Cancer Management ◽  
Non Invasive ◽  
Disease States ◽  
Free Dna

Cell-free DNA (cfDNA) has the potential to enable non-invasive detection of disease states and progression. Beyond its sequence, cfDNA also represents the nucleosomal landscape of cell(s)-of-origin and captures the dynamics of the epigenome. In this review, we highlight the emergence of cfDNA epigenomic methods that assess disease beyond the scope of mutant tumour genotyping. Detection of tumour mutations is the gold standard for sequencing methods in clinical oncology. However, limitations inherent to mutation targeting in cfDNA, and the possibilities of uncovering molecular mechanisms underlying disease, have made epigenomics of cfDNA an exciting alternative. We discuss the epigenomic information revealed by cfDNA, and how epigenomic methods exploit cfDNA to detect and characterize cancer. Future applications of cfDNA epigenomic methods to act complementarily and orthogonally to current clinical practices has the potential to transform cancer management and improve cancer patient outcomes.

scholarly journals The miR-582/CD1B Axis Is Involved in Regulation of Dendritic Cells and Is Associated with Clinical Outcomes in Advanced Lung Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jun Guo ◽  
Hui Jin ◽  
Yanfeng Xi ◽  
Jian Guo ◽  
Yi Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Lung Adenocarcinoma ◽  
Patient Outcomes ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Cell Types ◽  
Independent Dataset ◽  
Immune Genes ◽  
Novel Biomarkers

The involvement of immune dysfunction in the pathogenesis of lung cancer has been extensively studied. However, the potential molecular mechanisms through which the tumor immune response affects drug resistance are still unclear. Accordingly, in this study, we evaluated deviations in the immune cell landscape among patients with different stages of lung adenocarcinoma to identify key microRNAs and their targets associated with patient outcomes. CIBERSORT was used for estimating the proportions of immune cells in various lung tissues. Significantly different adaptive and innate immune cell types, including memory B cells, CD8+ T cells, resting dendritic cells, and resting mast cells, were selected. Comparative studies and survival analyses were carried out. We found that potential genes and microRNAs involved in immune responses were associated with patient outcomes. Specifically, miR-582/CD1B, which are involved in resting and activated dendritic cells, may be potential novel biomarkers for immunotherapy. An independent dataset of miRNA microarray profiles was used to validate the expression of mature miR-582-5p in patients with advanced lung adenocarcinoma. Alternative treatments, including immunotherapies and chemotherapy, are urgently needed to improve outcomes in patients with lung cancer. Thus, our findings could provide insights into the selection of novel microRNAs targeting immune genes and could improve the efficacy of immunotherapy by disrupting tumor function and promoting immune infiltration in patients with advanced lung adenocarcinoma.

scholarly journals Evolution of cellular morpho-phenotypes in cancer metastasis

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Pei-Hsun Wu ◽  
Jude M. Phillip ◽  
Shyam B. Khatau ◽  
Wei-Chiang Chen ◽  
Jeffrey Stirman ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Cell Contact ◽  
Morphological Variations ◽  
Local Cell ◽  
2D And 3D ◽  
Content Information

AbstractIntratumoral heterogeneity greatly complicates the study of molecular mechanisms driving cancer progression and our ability to predict patient outcomes. Here we have developed an automated high-throughput cell-imaging platform (htCIP) that allows us to extract high-content information about individual cells, including cell morphology, molecular content and local cell density at single-cell resolution. We further develop a comprehensive visually-aided morpho-phenotyping recognition (VAMPIRE) tool to analyze irregular cellular and nuclear shapes in both 2D and 3D microenvironments. VAMPIRE analysis of ~39,000 cells from 13 previously sequenced patient-derived pancreatic cancer samples indicate that metastasized cells present significantly lower heterogeneity than primary tumor cells. We found the same morphological signature for metastasis for a cohort of 10 breast cancer cell lines. We further decipher the relative contributions to heterogeneity from cell cycle, cell-cell contact, cell stochasticity and heritable morphological variations.

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