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  1. Article: Case Report: Dostarlimab for treatment of aggressive cutaneous squamous cell carcinoma.

    Gandarillas, Sophia / Tang, Horace / Dasgeb, Bahar

    Frontiers in medicine

    2024  Volume 11, Page(s) 1322210

    Abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy with the aggressive cSCC subtype being especially worrisome due to its higher metastatic and mortality rate. An 80-year-old immunocompetent Caucasian man presented with a ... ...

    Abstract Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy with the aggressive cSCC subtype being especially worrisome due to its higher metastatic and mortality rate. An 80-year-old immunocompetent Caucasian man presented with a locally advanced and recurrent cSCC for which he underwent six Mohs surgeries, radiation therapy, and standard immunotherapy treatments. Throughout treatment, the patient's cancer continued to progress across different regions of the face. Biopsy and analysis were performed and showed that the cSCCs had a high mutational burden and oncogenes known to be present in tumors with aggressive nature. After the algorithmically applied standard of care failed to cure or control the progressing disease, the genetic analysis favored dostarlimab as a suitable option. With only three doses of 500 mg dostarlimab q3 weeks, the patient showed a fast response with macroscopic resolution of clinically discernible disease of, the previously noted, locally advanced cSCC on his right forehead, as well as other primary keratinocyte carcinomas on his left contralateral face, nose, left leg, and neck. This remarkable case can present an option for complex patients with locally advanced and recurrent cSCC who failed the current standard of care. Moreover, it warrants a proper clinical trial to assess efficacy and potential indication of dostarlimab in such patients. Of note is the presence of a KMT2D mutation and its well-identified correlation with mismatch repair deficiency (dMMR) and poor prognosis, which can play an informative role in clinical decision making and precision therapeutic choice at the point of care.
    Language English
    Publishing date 2024-03-11
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2024.1322210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: HLA inherence as a potential parameter in checkpoint inhibitor-associated autoimmune adverse event assessment.

    Gandarillas, Sophia / Newland, Elizabeth Schoenberg / Toppmeyer, Deborah / Stephenson, Ryan / Denzin, Lisa / Dasgeb, Bahar

    Frontiers in medicine

    2024  Volume 10, Page(s) 1288844

    Abstract: Background: The success of immunotherapy has made it a lifesaving treatment, but not without side effects. Currently, the risk factors for developing immune-related adverse events (irAEs) in patients who receive immunotherapy are poorly understood, and ... ...

    Abstract Background: The success of immunotherapy has made it a lifesaving treatment, but not without side effects. Currently, the risk factors for developing immune-related adverse events (irAEs) in patients who receive immunotherapy are poorly understood, and there is no risk-stratifying mechanism for potentially fatal irAEs. It is postulated that oncology patients with preexisting autoimmune diseases are likely to have flares on immunotherapy. However, some patients develop
    Methods: The oncology patients who developed autoimmune adverse events on immunotherapy for whom the continuation of treatment was prudent or lifesaving were selected. Of note, all nine patients received checkpoint inhibitors (CIs). Of the nine selected patients, only one had a prior history of an autoimmune condition. None of the nine selected patients had an active autoimmune condition at the time of CI initiation. Their HLA was typed, and the results were cross-referenced with the literature reports in PubMed and Google search with the corresponding autoimmune condition of each patient.
    Results: Herein, we report nine patients with irAEs for whom retrospective HLA typing revealed the inherence of multiple related HLA alleles that may correspond to the autoimmune condition that they had developed on immunotherapy. It is to be mentioned that the inherence of enriched disease-related HLA alleles was shared among patients with the same irAEs. These patients developed a range of irAEs including bullous pemphigoid, pemphigus foliaceus/vulgaris, thyroiditis, vitiligo, and hepatitis on immunotherapy. Although some combinations of disease-related HLA were well reported in otherwise idiopathic autoimmune diseases, a frequently repeated HLA allele combination in our patient population was found to be rarely seen in the general population.
    Conclusion: The authors suggest that an enriched inherence of disease-related HLA alleles may play a role in the genetic propensity for the development of irAEs in oncology patients, who receive immunotherapy, including CIs. Inherence of more than one or a cluster of particular autoimmune disease-related HLA alleles in patients who receive immunotherapy may unmask the corresponding autoimmune disease as the genotype inherence presents with the phenotype of the corresponding condition. It is suggested that enriched linked HLA genotypes, which are otherwise rare in the general population, may present as the corresponding phenotype of the autoimmune condition. Such clinical presentation, enhanced by immunotherapy, such as CIs, can play a role in risk stratifying patients for precision medicine and improve the outcome.
    Language English
    Publishing date 2024-01-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1288844
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Next-generation sequencing in dermatology.

    King, Andrew D / Deirawan, Hany / Klein, Paytra A / Dasgeb, Bahar / Dumur, Catherine I / Mehregan, Darius R

    Frontiers in medicine

    2023  Volume 10, Page(s) 1218404

    Abstract: Over the past decade, Next-Generation Sequencing (NGS) has advanced our understanding, diagnosis, and management of several areas within dermatology. NGS has emerged as a powerful tool for diagnosing genetic diseases of the skin, improving upon ... ...

    Abstract Over the past decade, Next-Generation Sequencing (NGS) has advanced our understanding, diagnosis, and management of several areas within dermatology. NGS has emerged as a powerful tool for diagnosing genetic diseases of the skin, improving upon traditional PCR-based techniques limited by significant genetic heterogeneity associated with these disorders. Epidermolysis bullosa and ichthyosis are two of the most extensively studied genetic diseases of the skin, with a well-characterized spectrum of genetic changes occurring in these conditions. NGS has also played a critical role in expanding the mutational landscape of cutaneous squamous cell carcinoma, enhancing our understanding of its molecular pathogenesis. Similarly, genetic testing has greatly benefited melanoma diagnosis and treatment, primarily due to the high prevalence of BRAF hot spot mutations and other well-characterized genetic alterations. Additionally, NGS provides a valuable tool for measuring tumor mutational burden, which can aid in management of melanoma. Lastly, NGS demonstrates promise in improving the sensitivity of diagnosing cutaneous T-cell lymphoma. This article provides a comprehensive summary of NGS applications in the diagnosis and management of genodermatoses, cutaneous squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma, highlighting the impact of NGS on the field of dermatology.
    Language English
    Publishing date 2023-09-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1218404
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The potential role of HLA typing to risk stratify melanoma patients on immunotherapy with associated SJS: pitfalls and opportunities.

    Schoenberg, Elizabeth / Mehregan, Darius / Colombe, Beth / Hazan, Ezra / Dasgeb, Bahar

    International journal of dermatology

    2021  Volume 61, Issue 9, Page(s) e335–e337

    MeSH term(s) Anticonvulsants/adverse effects ; Genetic Predisposition to Disease ; Genotype ; HLA-B Antigens/genetics ; Histocompatibility Testing ; Humans ; Immunotherapy/adverse effects ; Melanoma/complications ; Melanoma/therapy ; Stevens-Johnson Syndrome/complications
    Chemical Substances Anticonvulsants ; HLA-B Antigens
    Language English
    Publishing date 2021-07-24
    Publishing country England
    Document type Letter
    ZDB-ID 412254-9
    ISSN 1365-4632 ; 0011-9059 ; 1461-1244
    ISSN (online) 1365-4632
    ISSN 0011-9059 ; 1461-1244
    DOI 10.1111/ijd.15794
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cutaneous Crohn's disease with superimposed psoriasis: A unique case with overlapping histology.

    Friedman, Ben J / Dasgeb, Bahar / Lee, Jason B

    Journal of cutaneous pathology

    2017  Volume 44, Issue 6, Page(s) 588–590

    Abstract: Crohn's disease (CD) is an idiopathic, chronic inflammatory disorder of the gastrointestinal tract. We recently encountered a unique case in which a patient with longstanding CD presented with skin lesions with histopathologic features of both psoriasis ... ...

    Abstract Crohn's disease (CD) is an idiopathic, chronic inflammatory disorder of the gastrointestinal tract. We recently encountered a unique case in which a patient with longstanding CD presented with skin lesions with histopathologic features of both psoriasis and granulomatous inflammation suggestive of cutaneous CD. To our knowledge, this has not been described concomitantly in the same patient, in the same lesions. Review of the literature suggests that the intersection of these 2 histopathological reaction patterns may not be pure coincidence. Clinical-pathologic correlation of this case will be discussed, along with a review of the potential mechanisms of this unique disease presentation.
    Language English
    Publishing date 2017-06
    Publishing country United States
    Document type Case Reports
    ZDB-ID 187078-6
    ISSN 1600-0560 ; 0303-6987
    ISSN (online) 1600-0560
    ISSN 0303-6987
    DOI 10.1111/cup.12928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cancer-testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities.

    Dasgeb, Bahar / Mehregan, Darius / Ring, Christina / Nartker, Nathan / Brownell, Isaac

    Journal of cutaneous pathology

    2019  Volume 46, Issue 10, Page(s) 748–752

    Abstract: Background: The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens imparts tumor specificity, making them ideal candidates for targeted immunotherapy. We ... ...

    Abstract Background: The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens imparts tumor specificity, making them ideal candidates for targeted immunotherapy. We investigate the usefulness of the CT antigens SPA17 (sperm protein-17 [SP-17]), IGF2BP3 (insulin-like growth factor-II mRNA-binding protein 3 [IMP-3]), and transmembrane protein with epidermal growth factor (EGF)-like and two follistatin-like domains 1 (TMEFF1) as potential MCC biomarkers and evaluate their possible utility in immunotherapy and molecularly targeted image-guided treatment.
    Methods: The CT antigens SP-17, IMP-3, and TMEFF1 were selected using transcriptome profiling to identify CT antigens expressed in MCC tumors. Antibodies directed against these CT antigens were stained. Twelve normal skin tissue samples were used as a control. The average percentage of positive cells in each tumor was computed.
    Results: Twelve of 14 (86%) MCC cases showed crisp nuclear staining for SP-17, with 2.06% of cells staining positive. IMP-3 showed crisp, perinuclear staining in all 14 MCC cases, with 52.93% MCC cells staining positive. TMEFF1 showed perinuclear staining in all 14 MCC cases, with 96.51% of tumor cells staining positive.
    Conclusions: CT antigens were found to be expressed in both MCC and some control tissues. SP-17 was the most specific yet the least sensitive. IMP-3 and TMEFF1 were both sensitive but not specific. CT antigens may represent valuable treatment targets in MCC.
    MeSH term(s) Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Merkel Cell/genetics ; Carcinoma, Merkel Cell/metabolism ; Carcinoma, Merkel Cell/pathology ; Cell Line, Tumor ; Humans ; Male ; Skin Neoplasms/genetics ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Testicular Neoplasms/genetics ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/pathology
    Chemical Substances Antigens, Neoplasm ; Biomarkers, Tumor
    Language English
    Publishing date 2019-07-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 187078-6
    ISSN 1600-0560 ; 0303-6987
    ISSN (online) 1600-0560
    ISSN 0303-6987
    DOI 10.1111/cup.13528
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Pemphigus associated with ipilimumab therapy.

    Schoenberg, Elizabeth / Colombe, Beth / Cha, Jisun / Orloff, Marlana / Shalabi, Doaa / Ross, Nicholas A / Dasgeb, Bahar

    International journal of dermatology

    2021  Volume 60, Issue 8, Page(s) e331–e333

    MeSH term(s) Humans ; Ipilimumab/adverse effects ; Melanoma/drug therapy ; Nivolumab ; Pemphigus/chemically induced ; Pemphigus/drug therapy
    Chemical Substances Ipilimumab ; Nivolumab (31YO63LBSN)
    Language English
    Publishing date 2021-01-07
    Publishing country England
    Document type Letter
    ZDB-ID 412254-9
    ISSN 1365-4632 ; 0011-9059 ; 1461-1244
    ISSN (online) 1365-4632
    ISSN 0011-9059 ; 1461-1244
    DOI 10.1111/ijd.15405
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non-syndromic basal cell carcinomas: The paradigm of oncogenic synergy.

    Dasgeb, Bahar / Pajouhanfar, Sara / Jazayeri, Ali / Schoenberg, Elizabeth / Kumar, Gaurav / Fortina, Paolo / Berger, Adam C / Uitto, Jouni

    Experimental dermatology

    2021  Volume 31, Issue 5, Page(s) 736–742

    Abstract: There has been a significant increase in basal cell carcinoma (BCC) incidence, the most common cancer in humans and the age of presentation with the first diagnosis of BCC has decreased in past decades. In this study, we investigated the possibility of ... ...

    Abstract There has been a significant increase in basal cell carcinoma (BCC) incidence, the most common cancer in humans and the age of presentation with the first diagnosis of BCC has decreased in past decades. In this study, we investigated the possibility of genetic markers that can lead to earlier and closer observation of patients at high risk for development of multiple BCCs. The overall goal is to decrease the morbidity and the economic burden of diagnosis and treatment of recurring and/or advanced BCCs. Four patients with numerous BCCs, some of them exceptionally large, were included in this study. A sample of representative BCCs, normal non-sun-exposed skin and blood samples were obtained from each patient. Whole-exome sequencing of DNA was conducted on all samples, and a series of bioinformatics filtering was performed to identify potentially pathogenic sequence variants. The analysis of the data resulted in detection of oncogenic mutations in PTCH1, two of which being novel, and concurrent mutations in TP53 in BCC tumours of all four patients. Such mutations may explain the numerous and postexcision recurring nature of the BCCs of exceptionally large size observed in all these patients, and they can be suggested to serve as a genetic marker for high-risk patients for early detection, prognostication and close follow-up.
    MeSH term(s) Carcinogenesis ; Carcinoma, Basal Cell/genetics ; Carcinoma, Basal Cell/pathology ; Humans ; Mutation ; Neoplasm Recurrence, Local ; Patched-1 Receptor/genetics ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Tumor Suppressor Protein p53/genetics
    Chemical Substances PTCH1 protein, human ; Patched-1 Receptor ; TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2021-12-17
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 1130936-2
    ISSN 1600-0625 ; 0906-6705
    ISSN (online) 1600-0625
    ISSN 0906-6705
    DOI 10.1111/exd.14510
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Impaired wound healing secondary to bevacizumab.

    Ahn, Ji W / Shalabi, Doaa / Correa-Selm, Lilia M / Dasgeb, Bahar / Nikbakht, Neda / Cha, Jisun

    International wound journal

    2019  Volume 16, Issue 4, Page(s) 1009–1012

    Abstract: Bevacizumab is a monoclonal antibody that exerts its antitumor activity by inhibiting vascular endothelial growth factor. Consequently, it suppresses endothelial cell proliferation, vascular permeability, and angiogenesis. This inhibitory effect ... ...

    Abstract Bevacizumab is a monoclonal antibody that exerts its antitumor activity by inhibiting vascular endothelial growth factor. Consequently, it suppresses endothelial cell proliferation, vascular permeability, and angiogenesis. This inhibitory effect contributes to tumour size reduction but causes wound-healing delay, specifically during the proliferative phase, in patients receiving bevacizumab. Although surgical wound-healing complications (WHC) associated with bevacizumab have been extensively reported, there is limited literature on peripheral WHC. More importantly, the histopathology of bevacizumab-associated WHC has not been described. We present the histopathology findings of a non-healing ulcer in a patient receiving bevacizumab, providing insight into the possible aetiology of this drug's adverse reaction. Furthermore, our patient's positive response to hyperbaric oxygen suggests its possible use for treatment of bevacizumab-associated non-healing wounds.
    MeSH term(s) Aged ; Angiogenesis Inhibitors/adverse effects ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/adverse effects ; Bevacizumab/therapeutic use ; Humans ; Male ; Pressure Ulcer/drug therapy ; Treatment Outcome ; Wound Healing/drug effects
    Chemical Substances Angiogenesis Inhibitors ; Bevacizumab (2S9ZZM9Q9V)
    Language English
    Publishing date 2019-05-21
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2170920-8
    ISSN 1742-481X ; 1742-4801
    ISSN (online) 1742-481X
    ISSN 1742-4801
    DOI 10.1111/iwj.13139
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Colchicine: an ancient drug with novel applications.

    Dasgeb, B / Kornreich, D / McGuinn, K / Okon, L / Brownell, I / Sackett, D L

    The British journal of dermatology

    2018  Volume 178, Issue 2, Page(s) 350–356

    Abstract: Colchicine is a treatment for gout that has been used for more than a millennium. It is the treatment of choice for familial Mediterranean fever and its associated complication, amyloidosis. The 2009 U.S. Food and Drug Administration approval of ... ...

    Abstract Colchicine is a treatment for gout that has been used for more than a millennium. It is the treatment of choice for familial Mediterranean fever and its associated complication, amyloidosis. The 2009 U.S. Food and Drug Administration approval of colchicine as a new drug had research consequences. Recent investigations with large cohorts of patients with gout who have been taking colchicine for years have demonstrated novel applications within oncology, immunology, cardiology and dermatology. Some emerging dermatological uses include the treatment of epidermolysis bullosa acquisita, leucocytoclastic vasculitis, aphthous stomatitis and others. In this work we relate the history and the new horizon of this ancient medicine.
    MeSH term(s) Colchicine/history ; Colchicine/pharmacology ; Colchicine/therapeutic use ; Dermatologic Agents/therapeutic use ; Familial Mediterranean Fever/drug therapy ; Gout/drug therapy ; Gout/history ; Gout Suppressants/history ; Gout Suppressants/pharmacology ; Gout Suppressants/therapeutic use ; History, 19th Century ; History, 21st Century ; History, Ancient ; Humans ; Rheumatic Diseases/drug therapy ; Skin Diseases/drug therapy ; Stomatitis, Aphthous/drug therapy ; Tubulin Modulators/pharmacology ; Tubulin Modulators/therapeutic use
    Chemical Substances Dermatologic Agents ; Gout Suppressants ; Tubulin Modulators ; Colchicine (SML2Y3J35T)
    Language English
    Publishing date 2018-01-03
    Publishing country England
    Document type Historical Article ; Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1111/bjd.15896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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