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  1. Article: Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

    Detrés Román, Carlos R / Rudloff, Michael W / Revetta, Frank / Favret, Natalie R / Murray, Kristen A / Roetman, Jessica J / Erwin, Megan M / Washington, Mary K / Philip, Mary

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however only a subset of patients with certain types of cancer achieves durable remissions. Cancer vaccines are an attractive strategy ... ...

    Abstract Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however only a subset of patients with certain types of cancer achieves durable remissions. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically-relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation. We compared how tumor-specific CD8 T cells (TST) differentiate in mice with early sporadic lesions as compared to late lesions and tested how immunotherapeutic strategies, including vaccination and ICB, reprogram TST and impact liver cancer progression.
    Methods: Mice with a germline floxed allele of the SV40 large T antigen (TAG) undergo spontaneous recombination and activation of the TAG oncogene, leading to rare early pre-cancerous lesions that inevitably progress to established liver cancer. We assessed the immunophenotype and function of TAG-specific CD8 T cells in mice with early and late liver lesions. We vaccinated mice, either alone or in combination with ICB, to test whether these immunotherapeutic interventions could stop liver cancer progression.
    Results: In mice with early lesions, a subset of TST were PD1
    Conclusion: Vaccination, but not ICB, generated a population of progenitor TST and halted cancer progression in a clinically relevant model of sporadic liver cancer. In patients with early cancers or at high-risk of cancer recurrence, immunization may be the most effective strategy.
    What is already known on this topic: Immunotherapy, including immune checkpoint blockade and cancer vaccines, fails to induce long-term remissions in most patients with cancer.
    What this study adds: Hosts with early lesions but not hosts with advanced cancer retain a progenitor TCF1+ TST population. This population can be reprogrammed and therapeutically exploited by vaccination, but not ICB, to block tumor progression.
    How this study might affect research practice or policy: For people at high-risk of cancer progression, vaccination administered when a responsive progenitor TST population is present may be the optimal immunotherapy to induce long-lasting progression-free survival.
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.26.582064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Aortic Dissection Risk in Marfan Syndrome.

    Roman, Mary J / Devereux, Richard B

    Journal of the American College of Cardiology

    2020  Volume 75, Issue 8, Page(s) 854–856

    MeSH term(s) Aneurysm, Dissecting/diagnostic imaging ; Aneurysm, Dissecting/epidemiology ; Aneurysm, Dissecting/etiology ; DNA Mutational Analysis ; Fibrillin-1/genetics ; Genetic Variation ; Humans ; Marfan Syndrome/complications ; Marfan Syndrome/diagnosis
    Chemical Substances FBN1 protein, human ; Fibrillin-1
    Language English
    Publishing date 2020-03-13
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2019.12.042
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  3. Article ; Online: Hereditary thoracic aortic disease: How to save lives.

    Roman, Mary J / De Backer, Julie

    The Journal of thoracic and cardiovascular surgery

    2021  Volume 163, Issue 1, Page(s) 39–45

    MeSH term(s) Aorta, Thoracic/abnormalities ; Aorta, Thoracic/diagnostic imaging ; Aortic Aneurysm, Thoracic/etiology ; Aortic Aneurysm, Thoracic/therapy ; Aortic Diseases/congenital ; Aortic Diseases/diagnosis ; Aortic Diseases/genetics ; Aortic Diseases/surgery ; Early Diagnosis ; Genetic Testing/methods ; Humans ; Mass Screening/methods ; Medical History Taking/methods ; Preventive Health Services/methods ; Preventive Health Services/organization & administration ; Time-to-Treatment
    Language English
    Publishing date 2021-02-02
    Publishing country United States
    Document type Editorial
    ZDB-ID 3104-5
    ISSN 1097-685X ; 0022-5223
    ISSN (online) 1097-685X
    ISSN 0022-5223
    DOI 10.1016/j.jtcvs.2021.01.075
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  4. Article ; Online: Bicuspid Aortic Valve in Marfan Syndrome.

    Braverman, Alan C / Roman, Mary J

    Circulation. Cardiovascular imaging

    2019  Volume 12, Issue 3, Page(s) e008860

    MeSH term(s) Aorta ; Aortic Valve/abnormalities ; Bicuspid Aortic Valve Disease ; Heart Valve Diseases ; Humans ; Marfan Syndrome
    Language English
    Publishing date 2019-03-03
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2435045-X
    ISSN 1942-0080 ; 1941-9651
    ISSN (online) 1942-0080
    ISSN 1941-9651
    DOI 10.1161/CIRCIMAGING.119.008860
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  5. Article ; Online: A wide QRS complex tachycardia: What is the mechanism?

    Patel, Rohan K / Roman, Mary J / Lerman, Bruce B / Cheung, Jim W

    Heart rhythm

    2020  Volume 17, Issue 5 Pt A, Page(s) 831–832

    MeSH term(s) Electrocardiography ; Heart Conduction System/physiopathology ; Heart Rate/physiology ; Humans ; Male ; Tachycardia, Atrioventricular Nodal Reentry/physiopathology ; Young Adult
    Language English
    Publishing date 2020-04-30
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2229357-7
    ISSN 1556-3871 ; 1547-5271
    ISSN (online) 1556-3871
    ISSN 1547-5271
    DOI 10.1016/j.hrthm.2019.12.014
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  6. Article ; Online: Hallmarks of CD8

    Rudloff, Michael W / Zumbo, Paul / Favret, Natalie R / Roetman, Jessica J / Detrés Román, Carlos R / Erwin, Megan M / Murray, Kristen A / Jonnakuti, Sriya T / Dündar, Friederike / Betel, Doron / Philip, Mary

    Nature immunology

    2023  Volume 24, Issue 9, Page(s) 1527–1539

    Abstract: Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. ...

    Abstract Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. However, we know little about the interplay between CD8
    MeSH term(s) Mice ; Animals ; CD8-Positive T-Lymphocytes ; Neoplasms ; Cell Division ; Antigens, Neoplasm ; Chromatin ; Receptors, Antigen, T-Cell
    Chemical Substances Antigens, Neoplasm ; Chromatin ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-08-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01578-y
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  7. Article: Lonidamine Induced Selective Acidification and De-Energization of Prostate Cancer Xenografts: Enhanced Tumor Response to Radiation Therapy.

    Orlovskiy, Stepan / Gupta, Pradeep Kumar / Roman, Jeffrey / Arias-Mendoza, Fernando / Nelson, David S / Koch, Cameron J / Narayan, Vivek / Putt, Mary E / Nath, Kavindra

    Cancers

    2024  Volume 16, Issue 7

    Abstract: Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard ... ...

    Abstract Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive
    Language English
    Publishing date 2024-03-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16071384
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  8. Article ; Online: Risk of Type B Dissection in Marfan Syndrome: The Cornell Aortic Aneurysm Registry.

    Narula, Nupoor / Devereux, Richard B / Arbustini, Eloisa / Ma, Xiaoyue / Weinsaft, Jonathan W / Girardi, Leonard / Malonga, Grace P / Roman, Mary J

    Journal of the American College of Cardiology

    2023  

    Abstract: Background: With preventive aortic grafting decreasing the incidence of type A dissections in Marfan syndrome (MFS), most dissections are now type B, for which risk factors remain largely uncertain.: Objectives: We explored the determinants of type B ...

    Abstract Background: With preventive aortic grafting decreasing the incidence of type A dissections in Marfan syndrome (MFS), most dissections are now type B, for which risk factors remain largely uncertain.
    Objectives: We explored the determinants of type B dissection risk in a large, single-center MFS registry.
    Methods: Demographic and anthropometric features, cardiovascular disease, and surgical history were compared in patients with MFS with and without type B dissection.
    Results: Of 336 patients with MFS, 47 (14%) experienced a type B dissection (vs type A in 9%). Patients with type B dissection were more likely to have undergone elective aortic root replacement (ARR) (79 vs 46%; P < 0.001). Of the patients, 55% had type B dissection a mean of 13.3 years after ARR, whereas 45% experienced type B dissection before or in the absence of ARR; 41 patients (87%) were aware of their MFS diagnosis before type B dissection. Among those with predissection imaging, the descending aorta was normal or minimally dilated (<4.0 cm) in 88%. In multivariable analyses, patients with type B dissection were more likely to have undergone ARR and independent mitral valve surgery, to have had a type II dissection, and to have lived longer.
    Conclusions: In our contemporary cohort, type B dissections are more common than type A dissections and occur at traditional nonsurgical thresholds. The associations of type B dissection with ARR, independent mitral valve surgery, and type II dissection suggest a more severe phenotype in the setting of prolonged life expectancy.
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2023.08.055
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  9. Article ; Online: Association of central and peripheral pulse pressure with intermediate cardiovascular phenotypes.

    Roman, Mary J

    Journal of hypertension

    2012  Volume 30, Issue 4, Page(s) 834–5; author reply 835

    MeSH term(s) Blood Pressure ; Female ; Heart Rate ; Humans ; Hypertension/physiopathology ; Male
    Language English
    Publishing date 2012-04
    Publishing country England
    Document type Comment ; Letter
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0b013e328350e569
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  10. Article ; Online: BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution.

    Tsukada, Kaima / Jones, Samuel E / Bannister, Julius / Durin, Mary-Anne / Vendrell, Iolanda / Fawkes, Matthew / Fischer, Roman / Kessler, Benedikt M / Chapman, J Ross / Blackford, Andrew N

    Molecular cell

    2024  Volume 84, Issue 4, Page(s) 640–658.e10

    Abstract: The Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1, and RMI2 to form the BTR complex, which dissolves double Holliday junctions and DNA replication intermediates to promote sister chromatid disjunction before cell division. ... ...

    Abstract The Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1, and RMI2 to form the BTR complex, which dissolves double Holliday junctions and DNA replication intermediates to promote sister chromatid disjunction before cell division. In its absence, structure-specific nucleases like the SMX complex (comprising SLX1-SLX4, MUS81-EME1, and XPF-ERCC1) can cleave joint DNA molecules instead, but cells deficient in both BTR and SMX are not viable. Here, we identify a negative genetic interaction between BLM loss and deficiency in the BRCA1-BARD1 tumor suppressor complex. We show that this is due to a previously overlooked role for BARD1 in recruiting SLX4 to resolve DNA intermediates left unprocessed by BLM in the preceding interphase. Consequently, cells with defective BLM and BRCA1-BARD1 accumulate catastrophic levels of chromosome breakage and micronucleation, leading to cell death. Thus, we reveal mechanistic insights into SLX4 recruitment to DNA lesions, with potential clinical implications for treating BRCA1-deficient tumors.
    MeSH term(s) Humans ; DNA/genetics ; DNA Repair ; DNA Replication ; DNA, Cruciform ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Recombinases/genetics ; RecQ Helicases/genetics ; RecQ Helicases/metabolism
    Chemical Substances DNA (9007-49-2) ; DNA, Cruciform ; DNA-Binding Proteins ; Recombinases ; RecQ Helicases (EC 3.6.4.12) ; BARD1 protein, human (EC 2.3.2.27) ; BRCA1 protein, human ; Bloom syndrome protein (EC 3.6.1.-)
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2023.12.040
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