César A. Virgen

Harvard University

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Nicole R. LeBoeuf

Harvard University

Cecilia Larocca

Harvard University

Jordan T. Said

Harvard University

Mario E. Lacouture

NYU Langone Health

Viswanath Reddy Belum

San Francisco General Hospital

Thomas S. Kupper

Brigham and Women's Hospital

Christina N. Kraus

University of California, Irvine

Paul D. Bieniasz

Rockefeller University

Ashley Elsensohn

Loma Linda University

David C. Fisher

Dana-Farber Cancer Institute

Cooperative Institutions

Harvard University

Brigham and Women's Hospital

Dana-Farber Cancer Institute

Dana-Farber Brigham Cancer Center

University of Adelaide

Massachusetts General Hospital

Universidade de São Paulo

Cornell University

University of California, San Diego

University of Toronto

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565 The microbial flora of taxane therapy-associated nail disease in cancer patients

Journal of Investigative Dermatology (2017)

César A. Virgen Viswanath Reddy Belum Mini Kamboj SB Goldfarb Victoria Blinder

Taxane

Onycholysis

Nail disease

Microbiological culture

10.1016/j.jid.2017.02.587

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Citations (0)

THE PROLONGED HOSPITAL COURSE OF A 59-YEAR-OLD MALE WITH STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS-LIKE ERUPTION ASSOCIATED WITH NIVOLUMAB THERAPY FOR METASTATIC MELANOMA

César A. Virgen Dong Joon Kim

Immune checkpoint inhibitors are associated with a variety of dermatologic immune-related adverse events (irAEs).These irAEs diminish patients' quality of life and in some cases lead to discontinuation of cancer therapy.In this report, we describe the 70-day hospital stay of a patient with SJS/TENlike eruption associated with nivolumab use for the treatment of metastatic melanoma.The rash developed 16 days after the initial dose of nivolumab.PMH: Metastatic melanoma, hypertension, "erythroderma-like rash on arms/back […] face/legs spared" (treated with Prednisone taper, stopped two weeks before the start of immunotherapy).Medications:

Toxic Epidermal Necrolysis

10.26226/morressier.5cdbe0aa618793e647b12ad2

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THE MICROBIAL FLORA OF CLINICALLY INFECTED CUTANEOUS METASTASES

César A. Virgen

Flora

10.26226/morressier.5cdbe0ab618793e647b12b02

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Author response

Annals of Allergy Asthma & Immunology (2020)

Désirée Larenas‐Linnemann Sergio de Jesús Romero Tapia César A. Virgen Javier Mallol Manuel Antonio Baeza Bacab

Wheeze

10.1016/j.anai.2020.05.010

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Primate Lentivirus Capsid Sensitivity to TRIM5 Proteins

Journal of Virology (2008)

Zerina Kratovac César A. Virgen Frederick Bibollet-Ruche Beatrice H. Hahn Paul D. Bieniasz

ABSTRACT Mammalian cells express several factors that inhibit lentiviral infection and that have been under strong selective pressure. One of these factors, TRIM5, targets the capsid protein of incoming retrovirus particles and inhibits subsequent steps of the replication cycle. By substituting human immunodeficiency virus type 1 capsid, we were able to show that a set of divergent primate lentivirus capsids was generally not susceptible to restriction by TRIM5 proteins from higher primates. TRIM5α proteins from other primates exhibited distinct restriction specificities for primate lentivirus capsids. Finally, we identified novel primate lentiviral capsids that are targeted by TRIMCyp proteins.

10.1128/jvi.00410-08

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Citations (52)

Vulvar squamous cell carcinoma guidelines do not include tissue-sparing techniques as a treatment option

International Journal of Women’s Dermatology (2023)

César A. Virgen Isabella I. Sanchez Ashley Elsensohn Christina N. Kraus

What is known about this subject in regard to women and their families? Current National Comprehensive Cancer Network guidelines for early-stage vulvar squamous cell carcinoma (SCC; T1a ≤1 mm invasion) and high-grade squamous intraepithelial lesion recommend wide local excision (at least 1 cm) as the primary treatment modality. Current excisional margins are often associated with disfigurement and functional deficits with psychologic, social, and sexual ramifications. What is new from this article as messages for women and their families? We propose a new category of very early vulvar SCC (high-grade squamous intraepithelial lesion, differentiated vulvar intraepithelial neoplasia, T1a) to be considered in vulvar cancer treatment guidelines that would include vulvar organ-sparing approaches. Tissue-sparing procedures dermatologists commonly utilize may be reasonable treatment modalities for some patients with very early vulvar SCC. We aim to bring increased awareness to the role tissue-sparing approaches can play in very early vulvar SCC and their utility in preserving vulvar function and preventing morbidity. National Comprehensive Cancer Network (NCCN) guidelines for early-stage vulvar squamous cell carcinoma (SCC; T1a ≤1 mm invasion) recommend wide local excision (WLE) as the primary treatment modality.1 The guidelines incorporate a footnote on high-grade squamous intraepithelial lesions (HSIL) and recommend WLE for these lesions as well. For these early-stage SCCs, there is no recommendation for sentinel lymph node biopsy or lymphadenectomy as the risk of nodal metastases is less than 1%.1 The guidelines on margin control for WLE state that efforts should be made to obtain surgical margins (at least 1 cm) at time of primary surgery. However, the guidelines also highlight that studies have called into question these margins, suggesting narrower margins as current excisional margins are often associated with disfigurement and functional deficits with psychologic, social, and sexual ramifications.2,3 There is precedence for inclusion of tissue-sparing procedures in NCCN guidelines previously. For example, Penile Cancer guidelines include a section on "Principles of Penile Organ-Sparing Approaches" as well as "Primary Radiation/Chemoradiation Therapy (Penile Preservation)" which state that Tis, Ta, and T1 penile cancer may be amenable to conservative modalities, including topical therapy, WLE, laser therapy, glansectomy, external beam radiation therapy, brachytherapy, and Mohs micrographic surgery (MMS). Topical regimens, laser devices, and settings are included. We suggest that the management of some cases of early vulvar SCC could benefit from an interdisciplinary approach between dermatology and gynecologic oncology. As NCCN Vulvar Cancer guidelines do not include tissue-sparing techniques for vulvar SCC, and dermatologists are not currently represented on the guideline committee, gynecologists may be less comfortable referring a patient for multidisciplinary evaluation with dermatology. However, the tissue-sparing procedures dermatologists commonly utilize may be reasonable treatment modalities for some patients with very early vulvar SCC, where larger excisions may be associated with increased morbidity. Such procedures may have utility for the following: HSIL, HPV-independent differentiated vulvar intraepithelial neoplasia, and T1a vulvar SCC. For example, reports available on use of MMS for select cases of SCC have found this may be an effective modality as a first-line therapy in select cases and in some treatment-refractory cases: 38 cases of vulvar SCC were treated with MMS with 4 reporting recurrence, however most cases were not early SCC, as the average tumor size was 18 mm and multiple had been treated with prior modalities including excision.4 Unfortunately, prospective studies on MMS for early vulvar SCC are lacking. Future studies should focus on efficacy and patient-reported outcomes with use of other tissue-sparing modalities for early vulvar SCC. Herein, we propose a new category of very early vulvar SCC (HSIL, differentiated vulvar intraepithelial neoplasia, T1a) to be considered in vulvar cancer treatment guidelines that would include vulvar-organ sparing approaches (Fig. 1). We aim to bring increased awareness to the role tissue-sparing approaches can play in very early vulvar SCC and their utility in preserving vulvar function and preventing morbidity. We encourage increased multidisciplinary collaboration between dermatology, gynecology, and other pertinent specialties to consider incorporation of tissue-sparing modalities into future guidelines, providing additional treatment options for patients with a diagnosis of very early vulvar SCC.Fig. 1.: Current and proposed NCCN Guidelines for vulvar SCC. *Special circumstances may allow the use of topical, laser, or radiation therapy. NCCN, National Comprehensive Cancer Network; SCC, squamous cell carcinoma; EBRT, external beam radiation therapy; HSIL, high-grade squamous intraepithelial lesions; dVIN, differentiated vulvar intraepithelial neoplasia; ILN, inguinal lymph nodes.Conflicts of interest None. Funding None. Study approval N/A. Author contributions CAV: Participated in writing of the paper and manuscript preparation. IIS: Participated in figure design and manuscript preparation. ANE: Participated in writing of the paper and manuscript preparation. CNK: Participated in writing of the paper and manuscript preparation.

Wide local excision

Vulvar intraepithelial neoplasia

Vulvar neoplasm

Squamous intraepithelial lesion

Vulvar Carcinoma

10.1097/jw9.0000000000000078

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Citations (2)

Independent genesis of chimeric TRIM5-cyclophilin proteins in two primate species

Proceedings of the National Academy of Sciences (2008)

César A. Virgen Zerina Kratovac Paul D. Bieniasz Théodora Hatziioannou

The host range of retroviruses is influenced by antiviral proteins such as TRIM5, a restriction factor that recognizes and inactivates incoming retroviral capsids. Remarkably, in Owl monkeys (omk), a cyclophilin A (CypA) cDNA has been transposed into the TRIM5 locus, resulting in the expression of a TRIM5-CypA fusion protein (TRIMCyp) that restricts retroviral infection based on the retroviral capsid-binding specificity of CypA. Here, we report that the seemingly improbable genesis of TRIMCyp has, in fact, occurred twice, and pigtailed macaques (pgt) express an independently generated TRIMCyp protein. The omkTRIMCyp and pgtTRIMCyp proteins restrict infection by several lentiviruses, but their specificities are distinguishable. Surprisingly, pgtTRIMCyp cannot bind to or restrict HIV-1 capsids as a consequence of a point mutation close to the Cyp:capsid-binding interface that was acquired during or after transposition of pgtCypA. However, the same mutation confers on pgtTRIMCyp the ability to restrict FIV in the presence of cyclosporin A, a drug that normally abolishes the interaction between pgtTRIMCyp or omkTRIMCyp and lentiviral capsids. Overall, an intuitively unlikely evolutionary event has, in fact, occurred at least twice in primates and represents a striking example of convergent evolution in divergent species.

Cypa

Cis-trans-Isomerases

Cyclophilin

10.1073/pnas.0709258105

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Citations (193)

Mogamulizumab-Associated Myositis With and Without Myasthenia Gravis and/or Myocarditis in Patients With T-Cell Lymphoma

The Oncologist (2023)

César A. Virgen Jeffrey A. Sparks Anju Nohria Méabh O’Hare Amrita Goyal

Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular immune-related adverse events (irAEs) associated with mogamulizumab in patients with T-cell lymphoma followed at Dana-Farber Cancer Institute from January 2015 to June 2022. We identified 5 cases of mogamulizumab-associated myositis and/or myocarditis (MAM/Mc), 2 additionally affected by myasthenia gravis, among 42 patients with T-cell lymphoma. Three cases experienced -mogamulizumab-associated rash (MAR) prior to developing MAM/Mc. The incidence (n = 5/42, 11.9%) of muscular mogamulizumab-associated irAEs may be higher than has been previously reported in clinical trials and may be of late onset (a median of 5 cycles and as late as 100 days from the last infusion). We highlight the utility of IVIG, together with systemic corticosteroids, for the treatment of these potentially fatal side effects associated with mogamulizumab therapy.

10.1093/oncolo/oyad155

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Citations (4)

Risk factors for wheezing in primary health care settings in the tropics

Annals of Allergy Asthma & Immunology (2019)

Désirée Larenas‐Linnemann Sergio Jesús Romero-Tapia César A. Virgen Javier Mallol Manuel Antonio Baeza Bacab

Wheeze

Univariate analysis

Attendance

10.1016/j.anai.2019.11.008

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Citations (8)