Circadian Biology and Stroke

Stroke ◽  
2021 ◽  
Author(s):  
Eng H. Lo ◽  
Gregory W. Albers ◽  
Martin Dichgans ◽  
Geoffrey Donnan ◽  
Elga Esposito ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Response To Therapy ◽  
Clinical Consequences ◽  
Physiological Pathways ◽  
Injury Recovery ◽  
Almost All ◽  
Circadian Biology

Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to connect molecular, cellular, and physiological pathways in circadian biology to clinical consequences in stroke. Accounting for the complex and multifactorial effects of circadian rhythm may improve translational opportunities for stroke diagnostics and therapeutics.

scholarly journals PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 266
Author(s):  
Juan Alfonso Redondo ◽  
Romain Bibes ◽  
Alizée Vercauteren Drubbel ◽  
Benjamin Dassy ◽  
Xavier Bisteau ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Circadian Rhythm ◽  
Survival Rate ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Response To Therapy ◽  
Circadian Oscillation ◽  
Resistance To Therapy

Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy.

Brain Tumor Reporting and Data System: A Pictorial Review

Neurographics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 175-185
Author(s):  
B. Rao ◽  
I. Ikuta ◽  
A. Mahajan ◽  
A.A. Karam ◽  
V.M. Zohrabian
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Response To Therapy ◽  
Data System ◽  
Imaging Features ◽  
New Paradigm ◽  
Advantages And Disadvantages ◽  
Pictorial Review ◽  
Almost All ◽  
The Brain

Brain tumors are a diverse group of neoplasms that are a source of substantial morbidity and mortality worldwide. Primary gliomas constitute almost all malignant brain tumors, with the most aggressive as well as most common form in adults, grade IV glioma or glioblastoma multiforme, carrying an especially poor prognosis. Neuroimaging is critical not only in the identification of CNS tumor but also in treatment-planning and assessing the response to therapy. Structured reporting continues to gain traction in radiology by reducing report ambiguity and improving consistency, while keeping referring clinicians and patients informed. The Brain Tumor Reporting and Data System (BT-RADS) is a relatively new paradigm that attempts to simplify and maximize consistency in radiologic reporting. BT-RADS incorporates MR imaging features, clinical assessment, and timing of therapy to assign each study a score or category, which is, in turn, linked to a management suggestion. The purpose of this pictorial review article is to familiarize radiologists and nonradiology neurologic specialists alike with BT-RADS, highlighting both advantages and limitations, in the hope that adoption of this system might ultimately facilitate more effective communication and improve consistency among reports.Learning Objective: To describe the features and underscore the advantages and disadvantages of the Brain Tumor Reporting and Data System (BT-RADS), a relatively new classification system that attempts to simplify and maximize consistency in radiologic reporting

Clonal hematopoiesis of indeterminate potential (CHIP) mutations in solid tumor malignancies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1507-1507
Author(s):  
Madison Conces ◽  
Ying Ni ◽  
Peter Bazeley ◽  
Bhumika Patel ◽  
Pauline Funchain ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lung Cancer ◽  
Solid Tumor ◽  
Hematological Malignancies ◽  
Response To Therapy ◽  
Original Research ◽  
Cardiac Events ◽  
Low Frequencies ◽  
Nccn Guidelines ◽  
Clinical Consequences

1507 Background: CHIP predisposes to a higher risk of developing hematological malignancies and cardiac events. Multiple germline mutations have been recognized as contributing to CHIP, most notably ASXL1, DNMT3A, and TET2. The frequency of CHIP mutations in solid tumor malignancies (STM) is unknown. We report the frequency and incidence of CHIP mutations in adult patients (pts) with STM. Methods: Data from 880 pts with STM who underwent next generation sequencing (NGS) at Foundation One from 2013-2017 was collected. This excluded two pts with known primary hematological malignancies who were removed. A list of CHIP mutations using NCCN guidelines as well as numerous original research articles was created, and tabulation of pathogenic or likely pathogenic mutations ( ASXL1, DNMT3A, TET2, JAK2, SF3B1, TP53, GNAS, N/KRAS) was performed. To date, only the lung, breast, and colorectal cancer pts have been annotated (N = 372) since these cancers have an overall higher incidence and prevalence in society. Results: Annotation of lung cancer pts (155/880), breast (118/880), and colorectal cancer pts (99/880) is collected and represents about 40% of all pts. At least one CHIP mutation was present in 44.5% (69/155) lung cancer pts, 32.2% (38/118) in breast cancer pts, and 7.1% (7/99) in colorectal cancer pts. Most common mutations found were TP53 and KRAS at 29.6% (110/372) and 28.0% (104/372), respectively. Mutations in genes not known to be somatic drivers for solid tumor malignancies, particularly SF3B1, DNMT3A, and JAK2, were found at very low frequencies 0.8% (3/372), 0.5% (2/372), and 0.3% (1/372), respectively. Notably, ASXL1 and TET2 mutations were not encountered in any pts. Conclusions: In tumor NGS testing, multiple CHIP mutations were noted to be present within the cohort of lung, breast, and colorectal cancers. There is a need to further understand clinical consequences of CHIP mutations incidentally found in pts with STM given known clinical implications of CHIP. We will report on clinical data (comorbidities), response/non-response to therapy, and identify specific molecular patterns of mutations to further understand the role of CHIP in pts with STM.

163 SEARCH FOR GENES OF WHICH THE AMOUNTS OF TRANSCRIPTS OSCILLATE EVERY 24 h IN THE MOUSE OVARY

2008 ◽  
Vol 20 (1) ◽  
pp. 161
Author(s):  
T. Amano ◽  
Y. Hatanaka ◽  
K. Saeki ◽  
Y. Hosoi ◽  
A. Iritani ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Circadian Rhythm ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Light Period ◽  
Vaginal Smear ◽  
Mouse Ovary ◽  
Circadian Genes ◽  
Ovarian Cells ◽  
Almost All

Perturbation of circadian rhythm is believed to be detrimental to the physiology of organs, including the mammalian ovary. However, the molecular mechanisms that are regulated by circadian rhythm in the ovary have not been identified. To identify the molecular mechanisms that are regulated by circadian rhythm and to speculate on the physiologies that are likely to be damaged by perturbation of circadian rhythm in the ovary, we searched for genes in which the amount of transcripts oscillates every 24 h in the mouse ovary. To achieve this, expression profiles of circadian genes (per1, per2, and bmal1) that code transcription-regulation factors for which transcription activities are known to oscillate every 24 h in almost all organs, and wee1, the transcription activity of which circadian genes regulate and which is known to elongate the G2 phase in the cell cycle, were analyzed in this study. Six-week-old female ICR mice were kept individually under a lighting schedule with lights on for 14 h followed by lights off for 10 h. A vaginal smear of each mouse was collected every day to determine its estrous cycle. Ovaries of 3 mice were collected continuously every 4 h over a 4-day period from the start of the light period on the day of proestrus. Total RNA was extracted from each ovary, and 500 ng each was used for cDNA synthesis. Transcripts of each gene and of tbp were quantified by real-time PCR, and the amount of the transcripts of each gene in each sample was divided by the amount of tbp transcripts. The obtained relative values in each sample were used as the representative data of the amount of transcripts of each gene. The amounts of per1, per2, and bmal1 clearly oscillated every 24 h. The maximum and minimum values of per1 and per2 were observed at 16 and 4 h, respectively, after onset of the light period each day. The maximum and minimum values of bmal1 were observed at the time of onset of the light period and at 12 h after onset of the light period each day. Averages of the maximum values of per1, per2, and bmal1 each day were significantly greater than averages of the minimum values (per1, 3.60 � 0.10 and 1.38 � 0.09; per2, 0.82 � 0.08 and 0.27 � 0.06; bmal1, 0.61 � 0.05 and 0.17 � 0.01; P < 0.05). The cyclicity in the oscillation of the amount of wee1 transcripts was weaker than that observed in circadian genes, but the average of values that were obtained from 12 to 20 h after onset of the light period each day was significantly greater than that obtained from 0 to 8 h (0.29 � 0.02 and 0.22 � 0.01; P < 0.05). Our results suggested that the cell cycle of ovarian cells is regulated in a circadian manner through wee1 transcription, which is regulated by circadian genes of which the amounts of transcripts oscillate every 24 h. Because an abnormal cell cycle seems to trigger the development of tumors or follicular cysts, perturbation of circadian rhythm may cause those ovarian diseases.

830 Combined Phototherapy and Melatonin for treatment of Circadian Rhythm Disorder in a Patient with Cornelia de Lange Syndrome

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A323-A324
Author(s):  
Hina Emanuel ◽  
Amee Revana ◽  
Tue Te ◽  
Kevin Kaplan
Keyword(s):  
Circadian Rhythm ◽  
Sleep Disorders ◽  
Low Dose ◽  
Light Therapy ◽  
Response To Therapy ◽  
Cornelia De Lange Syndrome ◽  
Wake Time ◽  
History Of ◽  
Cornelia De Lange ◽  
Circadian Rhythm Disorders

Abstract Introduction Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by variable physical, cognitive, and behavioral characteristics. Sleep disturbances have been frequently reported in CdLS including insomnia, sleep-disordered breathing, intrinsic sleep disorders, and circadian rhythm disorders (CRDs). The characterization and prevalence of CRDs in CdLS remain ill- defined. We report a case of a 13-year-old female with CdLS presenting with advanced sleep wake phase disorder (ASWPD). Report of case(s) A 13-year-old female with a past medical history of CdLS, developmental delay, bilateral cleft palate status post repair presents with inability to fall asleep at night and excessive daytime sleepiness.(EDS) Her sleep history consists of going to bed at 4 pm with no delayed sleep onset. She wakes at 2:30 am which has occurred since infancy. Mother reports the patient will remain awake from 2:30 am until she goes to school at 7:30 am. History is consistent with EDS and sleeping during the day while at school. Total sleep time of approximately 11–12 hours was reported in 24-hour period. History of obstructive sleep apnea, parasomnias, insomnia, restless leg syndrome, and psychotropic medications were not reported. Patient was treated with timed low dose melatonin therapy 0.5 mg at 4 pm and bright light therapy using 10,000 lux for 30 minutes at 7 am and 4 pm. Dim lights starting at 7:30 pm with structured scheduled sleep hygiene ensuring consistent bedtime at 9:30 pm. A consistent wake time at 7 am and no naps during the day was recommended. Follow up visits report successful response to therapy with attainment of desired sleep wake rhythm (bedtime at 9:30 pm and wake time at 7 am) and resolution of sleepiness during the day. Our patient was able to be weaned off of melatonin and light therapy and her circadian rhythm remained entrained. Conclusion Patients with disorder such as CdLS are at risk for circadian rhythm disorders. Our patient responded well to treatment with combined timed phototherapy and low dose melatonin therapy. Better knowledge and characterization of typology of CRDs in CdLS patients could permit a more specific therapeutic approach to sleep disorders in this population. Support (if any) None

Common and Founder Mutations for Monogenic Traits in Sub-Saharan African Populations

2018 ◽  
Vol 19 (1) ◽  
pp. 149-175
Author(s):  
Amanda Krause ◽  
Heather Seymour ◽  
Michèle Ramsay
Keyword(s):  
Molecular Genetic ◽  
Black Families ◽  
Oculocutaneous Albinism ◽  
Sub Saharan Africa ◽  
Founder Mutations ◽  
Monogenic Diseases ◽  
African Populations ◽  
Clinical Consequences ◽  
Sub Saharan ◽  
Almost All

This review highlights molecular genetic studies of monogenic traits where common pathogenic mutations occur in black families from sub-Saharan Africa. Examples of founder mutations have been identified for oculocutaneous albinism, cystic fibrosis, Fanconi anemia, and Gaucher disease. Although there are few studies from Africa, some of the mutations traverse populations across the continent, and they are almost all different from the common mutations observed in non-African populations. Myotonic dystrophy is curiously absent among Africans, and nonsyndromic deafness does not arise from mutations in GJB2 and GJB7. Locus heterogeneity is present for Huntington disease, with two common triplet expansion loci in Africa, HTT and JPH3. These findings have important clinical consequences for diagnosis, treatment, and genetic counseling in affected families. We currently have just a glimpse of the molecular etiology of monogenic diseases in sub-Saharan Africa, a proverbial “ears of the hippo” situation.

Illicit drugs and cardiac arrhythmias in athletes

2007 ◽  
Vol 14 (4) ◽  
pp. 487-494 ◽  
Author(s):  
Francesco Furlanello ◽  
Laura Vitali Serdoz ◽  
Riccardo Cappato ◽  
Luigi De Ambroggi
Keyword(s):  
Cardiac Arrhythmias ◽  
Illicit Drugs ◽  
Sport Activity ◽  
Related Substances ◽  
Arrhythmogenic Effect ◽  
Wide Range ◽  
Clinical Consequences ◽  
World Anti Doping Agency ◽  
Almost All ◽  
Androgenic Steroids

The current management of athletes with cardiac arrhythmias has become complicated by the widespread use of illicit drugs, which can be arrhythmogenic. The World Anti-Doping Agency annually updates a list of prohibited substances and methods banned by the International Olympic Committee that includes different classes of substances namely, anabolic androgenic steroids, hormones and related substances, β2-agonists, diuretics, stimulants, narcotics, cannabinoids, glucocorticosteroids, alcohol, β-blockers and others. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular) that can even be lethal and which are frequently sport activity related. A large use of illicit drugs has been documented in competitive athletes, but the arrhythmogenic effect of specific substances is not precisely known. Precipitation of cardiac arrhythmias, particularly in the presence of a latent electrophysiologic substrate including some inherited cardiomyopathies, at risk of sudden death or due to long-term consumption of the substances, should raise the suspicion that illicit drugs may be a possible cause and lead cardiologists to investigate carefully this relationship and appropriately prevent the clinical consequences.

Isotretinoin in Severe, Recalcitrant Cystic Acne: A Review

1983 ◽  
Vol 17 (5) ◽  
pp. 329-333 ◽  
Author(s):  
Jean A. Rumsfield ◽  
Dennis P. West ◽  
C. S. Ted Tse ◽  
Margaret L. Eaton ◽  
Lisa A. Robinson
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Sebaceous Gland ◽  
Drug Response ◽  
Response To Therapy ◽  
Recommended Dosage ◽  
Sebum Production ◽  
Almost All ◽  
Patients Experience ◽  
Systemic Antibiotics

Isotretinoin, an isomer of retinoic acid, recently has been approved by the Food and Drug Administration for treatment of severe, recalcitrant acne. The most impressive effects include inhibition of sebum production and a reversible decrease in sebaceous gland size. Isotretinoin has proved to be an effective drug; response to therapy has been seen in virtually 100 percent of patients treated. Almost all patients experience reversible cutaneous and mucous-membrane symptoms while on isotretinoin treatment. Other common side effects include conjunctivitis (38 percent) and eye irritation (50 percent). The recommended dosage is 1–2 mg/kg/d for no longer than 16 weeks. Isotretinoin is currently the treatment of choice for severe, recalcitrant acne; however, because of potential side effects associated with retinoids, isotretinoin should be reserved for those patients who are unresponsive to conventional therapy, including topical and systemic antibiotics.

scholarly journals Urinary Exosomes

2009 ◽  
Vol 9 ◽  
pp. 1107-1118 ◽  
Author(s):  
Irena Dimov ◽  
Ljubinka Jankovic Velickovic ◽  
Vladisav Stefanovic
Keyword(s):  
Large Scale ◽  
Multivesicular Body ◽  
Cell Types ◽  
Response To Therapy ◽  
Tissue Samples ◽  
Disease Evolution ◽  
Urinary Exosomes ◽  
Cellular Source ◽  
Almost All

Exosomes are nanovesicles of endocytic origin that are secreted into the extracellular space or body fluids when a multivesicular body (MVB) fuses with the cell membrane. Interest in exosomes intensified after their description in antigen-presenting cells and the observation that they can significantly moderate immune responsesin vivo. In the past few years, several groups have reported on the secretion of exosomes by almost all cell types in an organism. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins, reflecting their cellular source. Major research efforts were put into their surprisingly various biological functions and in translating knowledge into clinical practice. Urine provides an exciting noninvasive alternative to blood or tissue samples as a potential source of disease biomarkers. Urinary exosomes (UE) became the subject of serious studies just a few years ago. A recent large-scale proteomics-based study of normal UE revealed a myriad of proteins, including disease-related gene products. Thus, UE have valuable potential as a source of biomarkers for early detection of various types of diseases, monitoring the disease evolution and/or response to therapy. As a relatively new field of research, it still faces many challenges, but UE have already shown some straightforward potential.

scholarly journals Recommended Usage of Epoetin Alpha Biosimilar Retacrit™: A Subanalysis of the Orheo Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1330-1330
Author(s):  
Mauricette Michallet ◽  
Pierre Soubeyran ◽  
Elisabeth Luporsi ◽  
Jean-Emmanuel Kurtz ◽  
Hélène Albrand
Keyword(s):  
Therapeutic Option ◽  
Stage Iv ◽  
Response To Therapy ◽  
Solid Tumours ◽  
Recommended Dose ◽  
Similar Proportion ◽  
Epoetin Alpha ◽  
Red Blood Cell Transfusions ◽  
Almost All

Abstract Introduction Chemotherapy-induced anaemia (CIA) is a frequent complication of patients (pts) with cancer, associated with fatigue and impaired quality of life, and may have serious medical consequences that can lead to discontinuation or interruption of chemotherapy (CT). Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend epoetin treatment of CIA to increase haemoglobin (Hb) levels and to help to prevent red blood cell transfusions and related complications. Several epoetin alpha biosimilars are currently approved for use in the EU for the treatment of CIA. The ORHEO study (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France that evaluated the changes in Hb level in pts with solid tumours, lymphoma or myeloma, treated with an epoetin alfa biosimilar (EAB). In this subanalysis of the ORHEO study, we compare the usage of EAB in relation to the dosage recommendations of the EORTC guidelines, with respect to efficacy and safety. Methods Pts >18 years with CIA (Hb <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for EAB treatment were included in this study. Pts were monitored at the start of EAB therapy (D0), at 3 months (M3) and 6 months (M6). Hb response was defined as achievement of target Hb without blood transfusions in the preceding 3 weeks and during treatment or Hb ≥10 g/dL or Hb increase ≥1 g/dL since inclusion. The prescribed dosage of EAB according to body weight and the tolerability of EAB at that recommended dosage were analysed at each time point. Results Data from 2310 pts (mean age ± standard deviation 66.5±11.8 years) from 232 centres were included in the study analysis. Overall, 79.6% of pts had solid tumours, 13.0% had lymphoma and 7.4% myeloma. Of those pts with solid tumours, 30.1% of pts had a stage III and 21.6% had a stage IV tumour. Mean baseline Hb level across all pts was 9.6 g/dL, with 35.6% of pts having moderate anaemia (Hb 8–9.5 g/dL). Almost all pts (99.9%) received the epoetin alpha biosimilar (Retacrit™, Hospira UK Ltd., median dose 30,000 IU/week). Overall, 43.8% of pts received the recommended dose of EAB (as determined by their weight) throughout the study. The proportion of pts receiving the recommended dose showed little variation between malignancies (lymphoma: 43.6%; myeloma: 40.9%; breast: 39.3%; lung: 48.3%; colorectal: 39.5%). Overall, the percentage of responders was 81.6% at M3 and 86.5% at M6. The overall mean change in Hb level was 1.5±1.6 g/dL at M3 and 1.72±1.61 g/dL at M6. Responses to treatment at M6 were similar whether or not EAB was prescribed at the recommended dose throughout the study. A similar proportion of pts receiving the recommended dose of EAB reported adverse events (AEs) at M6 compared with pts who did not receive the recommended dose (9.9 vs 9.0%). Overall, transfusion rates were 9.4% and 5.8%, while the rate of thromboembolic events was 2.4% and 1.5%, at 3 and 6 months respectively. Conclusion In the ORHEO study, 44% of pts received the EORTC recommended dose of EAB over the 6-month course of the study. However, the response to therapy was similar regardless of dose. Furthermore, the frequency of overall AEs at M6 did not vary depending on dose. In conclusion, the EAB Retacrit™ was effective and well tolerated in the management of CIA in pts with solid tumours, lymphoma and myeloma and provides an alternative therapeutic option for the treatment of CIA. Disclosures Michallet: MSD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hospira: Consultancy, Honoraria. Soubeyran:Roche: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria; Hospira: Honoraria. Kurtz:Hospira: Coverage of travel expenses/congress fees Other. Albrand:Hospira: Employment.

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