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  1. Article ; Online: The next generation of DNMT inhibitors.

    Mehdipour, Parinaz / Chen, Raymond / De Carvalho, Daniel D

    Nature cancer

    2022  Volume 2, Issue 10, Page(s) 1000–1001

    MeSH term(s) DNA (Cytosine-5-)-Methyltransferases/genetics ; Enzyme Inhibitors/pharmacology
    Chemical Substances Enzyme Inhibitors ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37)
    Language English
    Publishing date 2022-02-01
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2662-1347
    ISSN (online) 2662-1347
    DOI 10.1038/s43018-021-00271-z
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  2. Article ; Online: Endogenous retroelements as alarms for disruptions to cellular homeostasis.

    Lindholm, Håvard T / Chen, Raymond / De Carvalho, Daniel D

    Trends in cancer

    2022  Volume 9, Issue 1, Page(s) 55–68

    Abstract: Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that ... ...

    Abstract Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that disrupt the repression of endogenous retroelements show promise for treating cancer. Expressed endogenous retroelements can activate innate immune receptors that activate the antiviral response, potentially leading to the death of cancer cells. We discuss disruptions to cellular processes which can lead to activation of the antiviral state from endogenous retroelements, and present the 'fire alarm hypothesis', where we argue that endogenous retroelements act as alarms for disruptions to these cellular processes. Furthermore, we discuss the properties of endogenous retroelements which make them suitable as alarms.
    MeSH term(s) Humans ; Retroelements/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics ; Antiviral Agents ; Homeostasis/genetics
    Chemical Substances Retroelements ; Antiviral Agents
    Language English
    Publishing date 2022-10-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2852626-0
    ISSN 2405-8025 ; 2405-8033 ; 2405-8033
    ISSN (online) 2405-8025 ; 2405-8033
    ISSN 2405-8033
    DOI 10.1016/j.trecan.2022.09.001
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  3. Article: Management of Hyperhomocysteinemia, Low Vitamin Levels, and Low Cortisol in Cannabis Users: A Report of 2 Cases.

    de Carvalho, Jozélio / Lerner, Aaron / Feingold, Daniel

    Journal of chiropractic medicine

    2022  Volume 21, Issue 4, Page(s) 322–326

    Abstract: ... were given supplements of vitamins (folic acid, methylcobalamin, and pyridoxine), vitamin D ...

    Abstract Objective: The purpose of this study was to describe the management of 2 long-term users of cannabis with nutrition and psychotherapy.
    Clinical features: A 28-year-old man presented with a medical history of asthma, depression, anxiety, and smoking, and was a long-term user of cannabis for 9 years (usually 3 times a week). A 39-year-old man presented with a medical history of anxiety and fatigue, and was a long-term user of cannabis for 14 years (usually twice a week). Laboratory tests showed altered blood levels of homocysteine, vitamins, and cortisol.
    Intervention and outcome: Both patients were given supplements of vitamins (folic acid, methylcobalamin, and pyridoxine), vitamin D,
    Conclusion: This study describes vitamin deficiencies, low cortisol levels, and hyperhomocysteinemia in 2 cannabis users who were managed with a combination of nutritional supplements and psychotherapy.
    Language English
    Publishing date 2022-07-09
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2365038-2
    ISSN 1556-3715 ; 1556-3707
    ISSN (online) 1556-3715
    ISSN 1556-3707
    DOI 10.1016/j.jcm.2022.03.001
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  4. Article ; Online: Measuring the effect of drug treatments on primary human CD8+ T cell activation and cytolytic potential.

    Loo Yau, Helen / De Carvalho, Daniel D

    STAR protocols

    2021  Volume 2, Issue 2, Page(s) 100549

    Abstract: CD8+ T cells are key effector cells in adaptive immune responses against intracellular pathogens and cancer cells. Systemic drug treatments, like chemotherapy, may positively or negatively affect CD8+ T cell function. In this protocol, we describe robust ...

    Abstract CD8+ T cells are key effector cells in adaptive immune responses against intracellular pathogens and cancer cells. Systemic drug treatments, like chemotherapy, may positively or negatively affect CD8+ T cell function. In this protocol, we describe robust and optimized
    MeSH term(s) Antineoplastic Agents/pharmacology ; Biomarkers/analysis ; Biomarkers/metabolism ; CD8-Positive T-Lymphocytes/chemistry ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/metabolism ; Cell Separation/methods ; Cells, Cultured ; Cytokines/analysis ; Cytokines/metabolism ; Flow Cytometry/methods ; Humans
    Chemical Substances Antineoplastic Agents ; Biomarkers ; Cytokines
    Language English
    Publishing date 2021-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100549
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  5. Article: Efficacy and safety of transcranial direct current stimulation over the left dorsolateral prefrontal cortex in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, triple-blinded, sham-controlled, crossover trial.

    Guimarães, Rachel Silvany Quadros / Bandeira, Igor D / Barretto, Bianca Lima / Wanke, Thamires / Alves, Clara Oliveira Carvalho / Barretto, Thiago Lima / de Carvalho, Chrissie Ferreira / Dorea-Bandeira, Ingrid / Tolentino, Arthur / Lins-Silva, Daniel H / Lucena, Pedro H / Lucena, Rita

    Frontiers in psychiatry

    2024  Volume 14, Page(s) 1217407

    Abstract: Introduction: Although pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) has demonstrated efficacy, several individuals persist in experiencing social and academic impairment. Additionally, the occurrence of significant side ... ...

    Abstract Introduction: Although pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) has demonstrated efficacy, several individuals persist in experiencing social and academic impairment. Additionally, the occurrence of significant side effects may render the use of psychotropic medications untenable. However, Transcranial Direct Current Stimulation (tDCS), a non-invasive brain stimulation technique, shows promising results in treating ADHD.
    Objectives: To investigate the efficacy and safety of tDCS on the performance of children and adolescents with ADHD in neuropsychological tests involving visual attention, visual and verbal working memory, and inhibitory control.
    Methodology: This study was a triple-blind, randomized, sham-controlled, crossover clinical trial. The intervention consisted of a daily session of tDCS (2 mA) or sham targeting the left dorsolateral prefrontal cortex (L-DLPFC), for 30 min, on five consecutive days. The primary outcome was change in the Visual Attention Test, Fourth Edition (TAVIS-4) before and after each intervention. Subjects were also evaluated pre and post-tDCS using the Digit Span subtest of the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V), the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Inhibiting Response (IR) subtest, and the Corsi Block-Tapping Task.
    Results: Fifteen individuals were included, and no statistically significant difference was observed when comparing the results of the TAVIS-4, the IR of NEPSY-II, and the intragroup Digit Span subtest of WISC-V undertaken before and after the procedure. Adverse events were mainly self-limiting and transient. The participants did not perceive any benefit from tDCS when measured on the Patient Global Impression of Improvement (PGI-I) Scale.
    Conclusion: This study did not meet its primary endpoint and found no performance enhancement in any investigated neuropsychological outcomes relating to the intervention group.
    Language English
    Publishing date 2024-01-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2023.1217407
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  6. Article ; Online: Endogenous Retroelements and the Viral Mimicry Response in Cancer Therapy and Cellular Homeostasis.

    Chen, Raymond / Ishak, Charles A / De Carvalho, Daniel D

    Cancer discovery

    2021  Volume 11, Issue 11, Page(s) 2707–2725

    Abstract: Features of the cancer epigenome distinguish cancers from their respective cell of origin and establish therapeutic vulnerabilities that can be exploited through pharmacologic inhibition of DNA- or histone-modifying enzymes. Epigenetic therapies converge ...

    Abstract Features of the cancer epigenome distinguish cancers from their respective cell of origin and establish therapeutic vulnerabilities that can be exploited through pharmacologic inhibition of DNA- or histone-modifying enzymes. Epigenetic therapies converge with cancer immunotherapies through "viral mimicry," a cellular state of active antiviral response triggered by endogenous nucleic acids often derived from aberrantly transcribed endogenous retrotransposons. This review describes the initial characterization and expansion of viral mimicry-inducing approaches as well as features that "prime" cancers for viral mimicry induction. Increased understanding of viral mimicry in therapeutic contexts suggests potential physiologic roles in cellular homeostasis. SIGNIFICANCE: Recent literature establishes elevated cytosolic double strand RNA (dsRNA) levels as a cancer-specific therapeutic vulnerability that can be elevated by viral mimicry-inducing therapies beyond tolerable thresholds to induce antiviral signaling and increase dependence on dsRNA stress responses mediated by ADAR1. Improved understanding of viral mimicry signaling and tolerance mechanisms reveals synergistic treatment combinations with epigenetic therapies that include inhibition of BCL2, ADAR1, and immune checkpoint blockade. Further characterization of viral mimicry tolerance may identify contexts that maximize efficacy of conventional cancer therapies.
    MeSH term(s) Histones/genetics ; Homeostasis ; Humans ; Neoplasms/drug therapy ; Neoplasms/therapy ; RNA, Double-Stranded ; Retroelements
    Chemical Substances Histones ; RNA, Double-Stranded ; Retroelements
    Language English
    Publishing date 2021-10-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-21-0506
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6916: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Clinical advances in targeting epigenetics for cancer therapy.

    Feng, Shengrui / De Carvalho, Daniel D

    The FEBS journal

    2021  Volume 289, Issue 5, Page(s) 1214–1239

    Abstract: The appropriate coordination between epigenetic regulators is essential for spatial and temporal regulation of gene expression and maintenance of cell identity. Cancer is a disease driven by both genetic and epigenetic alterations. The widespread ... ...

    Abstract The appropriate coordination between epigenetic regulators is essential for spatial and temporal regulation of gene expression and maintenance of cell identity. Cancer is a disease driven by both genetic and epigenetic alterations. The widespread dysregulation and reversible nature of epigenetic alterations confer cancer cells with vulnerabilities for therapeutic interventions. Over the past decades, remarkable progress has been made in developing drugs that target epigenetic regulators, with many drugs under evaluation in clinical trials. Here, we summarize the epigenetic drugs currently in clinical investigations and highlight the potentials and challenges in their implication to treat cancer. We also discuss the preclinical and clinical results of combination therapies with epigenetic drugs and other therapies such as targeted and immune-based therapies.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Chromatin/chemistry ; Chromatin/drug effects ; Chromatin/immunology ; Combined Modality Therapy/methods ; DNA Methylation ; Drugs, Investigational/therapeutic use ; Epigenesis, Genetic ; Histones/antagonists & inhibitors ; Histones/genetics ; Histones/immunology ; Humans ; Immunotherapy/methods ; Molecular Targeted Therapy/methods ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/immunology ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/pathology ; Transcription, Genetic ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Chromatin ; Drugs, Investigational ; Histones ; Neoplasm Proteins
    Language English
    Publishing date 2021-02-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.15750
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 260: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  8. Article ; Online: Spliceosome-Targeted Therapies Induce dsRNA Responses.

    Ishak, Charles A / Loo Yau, Helen / De Carvalho, Daniel D

    Immunity

    2021  Volume 54, Issue 1, Page(s) 11–13

    Abstract: In a recent issue of Cell, Bowling et al. describe a mechanism by which spliceosome-targeted therapies result in intron-containing transcripts that form double-stranded RNAs (dsRNAs), thereby activating tumor antiviral signaling (viral mimicry) and ... ...

    Abstract In a recent issue of Cell, Bowling et al. describe a mechanism by which spliceosome-targeted therapies result in intron-containing transcripts that form double-stranded RNAs (dsRNAs), thereby activating tumor antiviral signaling (viral mimicry) and downstream adaptive immunity.
    MeSH term(s) Adaptive Immunity ; Antiviral Agents/pharmacology ; RNA, Double-Stranded ; Signal Transduction/drug effects ; Spliceosomes
    Chemical Substances Antiviral Agents ; RNA, Double-Stranded
    Language English
    Publishing date 2021-01-10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2020.12.012
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    Zs.A 4227: Show issues Location:
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    Zs.MG 69: Show issues

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  9. Article ; Online: DNA Methylation Profiling of Premalignant Lesions as a Path to Ovarian Cancer Early Detection.

    Ishak, Charles A / De Carvalho, Daniel D

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 23, Page(s) 6083–6085

    Abstract: Genome-wide DNA methylation profiles of serous tubal intraepithelial carcinomas (STIC) resemble methylation profiles of high-grade serous ovarian carcinomas (HGSOC) more closely than normal fallopian tube epithelium. While STICs and HGSOCs share subsets ... ...

    Abstract Genome-wide DNA methylation profiles of serous tubal intraepithelial carcinomas (STIC) resemble methylation profiles of high-grade serous ovarian carcinomas (HGSOC) more closely than normal fallopian tube epithelium. While STICs and HGSOCs share subsets of common hypermethylated regions, DNA methylation can distinguish STICs from HGSOCs to provide proof-of-principle that DNA methylation can identify HGSOC initiation.
    MeSH term(s) Carcinoma, Ovarian Epithelial/diagnosis ; Carcinoma, Ovarian Epithelial/genetics ; Cystadenocarcinoma, Serous/diagnosis ; Cystadenocarcinoma, Serous/genetics ; DNA Methylation ; Early Detection of Cancer ; Fallopian Tube Neoplasms ; Female ; Humans ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics
    Language English
    Publishing date 2020-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-3331
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    Zs.A 4223: Show issues Location:
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  10. Article: Clinical advances in targeting epigenetics for cancer therapy

    Feng, Shengrui / De Carvalho, Daniel D.

    FEBS journal. 2022 Mar., v. 289, no. 5

    2022  

    Abstract: The appropriate coordination between epigenetic regulators is essential for spatial and temporal regulation of gene expression and maintenance of cell identity. Cancer is a disease driven by both genetic and epigenetic alterations. The widespread ... ...

    Abstract The appropriate coordination between epigenetic regulators is essential for spatial and temporal regulation of gene expression and maintenance of cell identity. Cancer is a disease driven by both genetic and epigenetic alterations. The widespread dysregulation and reversible nature of epigenetic alterations confer cancer cells with vulnerabilities for therapeutic interventions. Over the past decades, remarkable progress has been made in developing drugs that target epigenetic regulators, with many drugs under evaluation in clinical trials. Here, we summarize the epigenetic drugs currently in clinical investigations and highlight the potentials and challenges in their implication to treat cancer. We also discuss the preclinical and clinical results of combination therapies with epigenetic drugs and other therapies such as targeted and immune‐based therapies.
    Keywords cancer therapy ; epigenetics ; gene expression regulation
    Language English
    Dates of publication 2022-03
    Size p. 1214-1239.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note REVIEW
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.15750
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