scholarly journals A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients

2021 ◽  
Author(s):  
Lasse D. Jensen ◽  
Delmy Oliva ◽  
Bengt-Åke Andersson ◽  
Freddi Lewin
Keyword(s):  
Cancer Patients ◽  
Current Knowledge ◽  
The Body ◽  
Circadian Disruption ◽  
Complex Interactions ◽  
Poor Treatment ◽  
Devices And Instruments ◽  
Multidisciplinary Perspective ◽  
Circadian Physiology ◽  
Metabolic Disruption

AbstractSleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and growing issue and at best a fractionated understanding of only part of the problem among researchers within each of these segments. Here, we take a multidisciplinary approach to comprehensively review the diagnosis and impact of sleep and circadian disruption in cancer patients. We discuss recent discoveries on molecular regulation of the circadian clock in healthy and malignant cells, the neurological and endocrine pathways controlling sleep and circadian rhythmicity, and their inputs to and outputs from the organism. The benefits and drawbacks of the various technologies, devices, and instruments used to assess sleep and circadian function, as well as the known consequences of sleep disruption and how sleep can be corrected in cancer patients, will be analyzed. We will throughout the review highlight the extensive crosstalk between sleep, circadian rhythms, and metabolic pathways involved in malignancy and identify current knowledge gaps and barriers for addressing the issue of sleep and circadian disruption in cancer patients. By addressing these issues, we hope to provide a foundation for further research as well as better and more effective care for the patients in the future.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

scholarly journals Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1408
Author(s):  
Hermann Brenner ◽  
Sabine Kuznia ◽  
Clarissa Laetsch ◽  
Tobias Niedermaier ◽  
Ben Schöttker
Keyword(s):  
Body Mass Index ◽  
Vitamin D ◽  
Cancer Patients ◽  
Body Mass ◽  
Advanced Cancer ◽  
Vitamin D3 ◽  
Normal Weight ◽  
The Body ◽  
Published Data ◽  
Vitamin D3 Supplementation

Meta-analyses of randomized controlled trials (RCTs) have demonstrated a protective effect of vitamin D3 (cholecalciferol) supplementation against cancer mortality. In the VITAL study, a RCT including 25,871 men ≥ 50 years and women ≥ 55 years, protective effects of vitamin D3 supplementation (2000 IU/day over a median of 5.3 years) with respect to incidence of any cancer and of advanced cancer (metastatic cancer or cancer death) were seen for normal-weight participants but not for overweight or obese participants. We aimed to explore potential reasons for this apparent variation of vitamin D effects by body mass index. We conducted complementary analyses of published data from the VITAL study on the association of body weight with cancer outcomes, stratified by vitamin D3 supplementation. Significantly increased risks of any cancer and of advanced cancer were seen among normal-weight participants compared to obese participants in the control group (relative risk (RR), 1.27; 95% confidence interval (CI), 1.07–1.52, and RR, 1.44; 95% CI, 1.04–1.97, respectively). No such patterns were seen in the intervention group. Among those with incident cancer, vitamin D3 supplementation was associated with a significantly reduced risk of advanced cancer (RR, 0.86; 95% CI, 0.74–0.99). The observed patterns point to pre-diagnostic weight loss of cancer patients and preventive effects of vitamin D3 supplementation from cancer progression as plausible explanations for the body mass index (BMI)—intervention interactions. Further research, including RCTs more comprehensively exploring the potential of adjuvant vitamin D therapy for cancer patients, should be pursued with priority.

scholarly journals Vascular endothelial cell specification in health and disease

Angiogenesis ◽  
2021 ◽  
Author(s):  
Corina Marziano ◽  
Gael Genet ◽  
Karen K. Hirschi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Current Knowledge ◽  
Vascular Malformations ◽  
Immune Surveillance ◽  
Vascular Endothelial Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
The Body ◽  
Vascular Networks

AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

scholarly journals Influence of Postoperative Changes in Sarcopenia on Long-Term Survival in Non-Metastatic Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2410
Author(s):  
Chungyeop Lee ◽  
In-Ja Park ◽  
Kyung-Won Kim ◽  
Yongbin Shin ◽  
Seok-Byung Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
The Body ◽  
Term Survival ◽  
Postoperative Changes ◽  
Asan Medical ◽  
Colorectal Cancer Patients

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.

scholarly journals Semen quality as a potential susceptibility indicator to SARS-CoV-2 insults in polluted areas

2021 ◽  
Author(s):  
Luigi Montano ◽  
Francesco Donato ◽  
Pietro Massimiliano Bianco ◽  
Gennaro Lettieri ◽  
Antonino Guglielmino ◽  
...  
Keyword(s):  
Semen Quality ◽  
Current Knowledge ◽  
Environmental Pollutants ◽  
Virus Transmission ◽  
Specific Area ◽  
The Body ◽  
Atmospheric Pollutants ◽  
Pollution Levels ◽  
Potential Indicator ◽  
Harmful Effects

AbstractThe epidemic of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impacted worldwide with its infectious spread and mortality rate. Thousands of articles have been published to tackle this crisis and many of these have indicated that high air pollution levels may be a contributing factor to high outbreak rates of COVID-19. Atmospheric pollutants, indeed, producing oxidative stress, inflammation, immuno-unbalance, and systemic coagulation, may be a possible significant co-factor of further damage, rendering the body prone to infections by a variety of pathogens, including viruses. Spermatozoa are extremely responsive to prooxidative effects produced by environmental pollutants and may serve as a powerful alert that signals the extent that environmental pressure, in a specific area, is doing damage to humans. In order to improve our current knowledge on this topic, this review article summarizes the relevant current observations emphasizing the weight that environmental pollution has on the sensitivity of a given population to several diseases and how semen quality, may be a potential indicator of sensitivity for virus insults (including SARS-CoV-2) in high polluted areas, and help to predict the risk for harmful effects of the SARS-CoV-2 epidemic. In addition, this review focused on the potential routes of virus transmission that may represent a population health risk and also identified the areas of critical importance that require urgent research to assess and manage the COVID-19 outbreak.

Microstructure of Carbon Black

1964 ◽  
Vol 37 (5) ◽  
pp. 1245-1298 ◽  
Author(s):  
F. A. Heckman
Keyword(s):  
Carbon Black ◽  
Gas Adsorption ◽  
Current Knowledge ◽  
Aggregate Size ◽  
Surface Characteristics ◽  
The Body ◽  
Degree Of Crystallinity ◽  
Complete Treatment ◽  
Real Value ◽  
Forms Of Carbon

Abstract Although the microstructure of carbon black has been under investigation for more than fifty years, there are still many aspects which are controversial and some which are virtually unexplored. The inherently low degree of crystallinity and the finely-divided state of carbon blacks have greatly hindered efforts to understand them. The purpose of this article is to cite the principal contributors to our understanding of carbon black microstructure, to discuss the significance of their contribution, to present a clear picture of the present state of our knowledge, and to note areas where controversy exists and where our knowledge is incomplete. The scope of this article is necessarily limited to a reasonably complete treatment of the several aspects of carbon black microstructure; that is, the arrangement of carbon atoms to form graphite layer planes, the arrangement of layer planes to form crystallites, and the arrangement of crystallites to form the more familiar carbon black “particles” or aggregates. Particular attention is paid to more recent articles and those which have shaped our thinking on carbon black microstructure. This article also includes a fairly complete review of various studies on the changes in microstructure which are brought about by heat treatment or oxidation. In general, the rather large number of studies reporting on the microstructure of other forms of carbon have not been reviewed (except for the work of Franklin whose contribution to our understanding of carbon-black microstructure is so immense that it must be included). Although gross, morphological features such as particle size, primary aggregate size and shape are studied briefly in order to relate them to microstructure, no effort was made to review comprehensively the body of literature pertinent to this subject. Also porosity and surface characteristics per se (as measured by gas adsorption techniques) are not treated in detail here. Rather than review a dreary list of papers which have only the slightest bearing on carbon black, the author has taken the liberty of dividing the articles reviewed into two categories. The first category, which is reviewed in some detail, includes those publications in which an important contribution was made to the understanding of carbon-black microstructure. The second category includes all those articles which are discussed only briefly or not at all because the authors have reported superficial or routine studies or they (probably unknown to them) have essentially duplicated the work of an earlier worker, or have reported uncorrected results which are thus so inaccurate as to be without real value to this article; or because they comprise work which is only peripherally related to carbon black microstructure. Also, references taken from other papers, but not reviewed here, are included in the latter category. Articles by Warren, Hofmann and Wilm, Steward and Cook and Walker contain bibliographies which will be helpful to those interested in the earlier work or in the microstructure of carbons other than carbon black. For the reader whose time is limited, an adequate picture of current understanding of carbon black microstructure can be gained by reading Sections II, IV, and V which are relatively short. Finally, a word about the spirit in which the review was written. At the request of the late Dr. Craig, a critical review was prepared in which every effort was made to point out shortcomings as well as classic contributions contained in the pertinent literature. Where the experts have disagreed, the reviewer, often with skill unequal to the task, has attempted to decide which one was the more correct in the light of current knowledge. It is with deep humility and great respect for those who have gone before that this review is submitted.

scholarly journals Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment

2021 ◽  
pp. 1-16
Author(s):  
Marcin Adamczak ◽  
Stanisław Surma
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Current Knowledge ◽  
Venous Blood ◽  
The Body ◽  
Hydrogen Ions ◽  
Ckd Progression ◽  
New Drug ◽  
Treatment And Prevention

<b><i>Background:</i></b> Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients. <b><i>Summary:</i></b> Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. <b><i>Key Message:</i></b> The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.

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