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Management of pigmented skin lesions during pregnancy

Friedman, Erica; Scolyer, Richard; Thompson, John
BACKGROUND:As a result of the rapidly changing hormonal milieu, changing or newly discovered pigmented skin lesions during pregnancy can be diagnostically challenging. It is important for GPs to be aware of the effect of gestational changes on pigment production and features that should raise concern. OBJECTIVE:The aim of this article is to provide an understanding of common changes that may occur in pigmented lesions during pregnancy, features that are of concern and the management of suspected melanoma in pregnant women. DISCUSSION:In pregnant women, changing naevi should be evaluated using conventional ABCDE melanoma diagnostic criteria, and suspicious lesions should not be attributed solely to a change in the hormonal milieu. In this population, diagnosed melanoma is probably best treated at a specialist centre.
PMID: 31476830
ISSN: 2208-7958
CID: 4068972

Appropriate excision margins for cutaneous melanomas

Thompson, John F; Friedman, Erica B
PMID: 31280970
ISSN: 1474-547x
CID: 3976322

Management of pigmented skin lesions in childhood and adolescence

Friedman, Erica B; Scolyer, Richard A; Thompson, John F
BACKGROUND:Pigmented skin lesions in childhood and adolescence can be diagnostically challenging. It is important for general practitioners to be aware of the spectrum of benign, atypical and malignant pigmented lesions occurring in these patient groups and of features that should raise concern. OBJECTIVE:The aims of this article are to assist recognition of high-risk skin lesions encountered in childhood and adolescence and to provide an understanding of the features and management of suspected melanoma in this population. DISCUSSION:In children and adolescents, there exist a variety of congenital and acquired naevi and other pigmented skin lesions that can be diagnostically problematic. Additionally, conventional detection criteria for melanoma seen in adults are often not present in children and adolescents, making diagnosis more difficult. Melanoma, if diagnosed in these populations, should be treated at a specialist centre whenever possible.
PMID: 31370129
ISSN: 2208-7958
CID: 4038402

When is surgery for metastatic melanoma still the most appropriate treatment option?

Friedman, Erica B; Ferguson, Peter M; Thompson, John F
PMID: 30071762
ISSN: 1744-8328
CID: 3242912

Continuing and new roles for surgery in the management of patients with stage IV melanoma [Editorial]

Friedman, Erica B; Thompson, John F
PMCID:6122527
PMID: 30190929
ISSN: 2045-0893
CID: 3663802

Association of melanoma expression of matrix metalloproteinase-23 with blunted tumor immunity and poor responses to immunotherapy. [Meeting Abstract]

Moogk, Duane; Li, Tianqi; Lee, Chelsea; Da Silva, Ines Esteves Domingues Pires; Ma, Michelle W; Friedman, Erica Brooke; De Miera, Eleazar Vega-Saenz; Darvishian, Farbod; Scanlon, Patrick; Perez-Garcia, Arianne; Pavlick, Anna C; Bhardwaj, Nina; Christos, Paul J; Osman, Iman; Krogsgaard, Michelle
ISI:000358036904074
ISSN: 1527-7755
CID: 1729922

Melanoma expression of matrix metalloproteinase-23 is associated with blunted tumor immunity and poor responses to immunotherapy

Moogk, Duane; da Silva, Ines; Ma, Michelle W; Friedman, Erica B; de Miera, Eleazar; Darvishian, Farbod; Scanlon, Patrick; Perez-Garcia, Arianne; Pavlick, Anna C; Bhardwaj, Nina; Christos, Paul J; Osman, Iman; Krogsgaard, Michelle
BackgroundMatrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca2+ signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma.MethodsWe characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression.ResultsOur data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P inverted question mark= inverted question mark0.05), in particular brisk TILs (P inverted question mark= inverted question mark0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T cells (P inverted question mark= inverted question mark0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P inverted question mark= inverted question mark0.037) but not in those treated with vaccines (P inverted question mark= inverted question mark0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P inverted question mark= inverted question mark0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P inverted question mark= inverted question mark0.27).ConclusionsOur data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.
PMCID:4272770
PMID: 25491880
ISSN: 1479-5876
CID: 1393652

Hedgehog pathway blockade inhibits melanoma cell growth in vitro and in vivo

O'Reilly, Kathryn E; de Miera, Eleazar Vega-Saenz; Segura, Miguel F; Friedman, Erica; Poliseno, Laura; Han, Sung Won; Zhong, Judy; Zavadil, Jiri; Pavlick, Anna; Hernando, Eva; Osman, Iman
Previous reports have demonstrated a role for hedgehog signaling in melanoma progression, prompting us to explore the therapeutic benefit of targeting this pathway in melanoma. We profiled a panel of human melanoma cell lines and control melanocytes for altered expression of hedgehog pathway members and determined the consequences of both genetic and pharmacological inhibition of the hedgehog pathway activator Smoothened (SMO) in melanoma, both in vitro and in vivo. We also examined the relationship between altered expression of hedgehog pathway mediators and survival in a well-characterized cohort of metastatic melanoma patients with prospectively collected follow up information. Studies revealed that over 40% of the melanoma cell lines examined harbored significantly elevated levels of the hedgehog pathway mediators SMO, GLI2, and PTCH1 compared to melanocytes (p < 0.05). SMO inhibition using siRNA and the small molecule inhibitor, NVP-LDE-225, suppressed melanoma growth in vitro, particularly in those cell lines with moderate SMO and GLI2 expression. NVP-LDE-225 also induced apoptosis in vitro and inhibited melanoma growth in a xenograft model. Gene expression data also revealed evidence of compensatory up-regulation of two other developmental pathways, Notch and WNT, in response to hedgehog pathway inhibition. Pharmacological and genetic SMO inhibition also downregulated genes involved in human embryonic stem cell pluripotency. Finally, increased SMO expression and decreased expression of the hedgehog pathway repressor GLI3 correlated with shorter post recurrence survival in metastatic melanoma patients. Our data demonstrate that hedgehog pathway inhibition might be a promising targeted therapy in appropriately selected metastatic melanoma patients.
PMCID:3854019
PMID: 24287465
ISSN: 1424-8247
CID: 688062

Screening Prior to Breast Cancer Diagnosis: The More Things Change, the More They Stay the Same [Meeting Abstract]

Friedman, Erica; Chun, Jennifer; Schnabel, Freya; Schwartz, Shira; Law, Sidney; Billig, Jessica; Ivanoff, Erin; Moy, Linda; Leite, Ana Paula; Axelrod, Deborah; Guth, Amber
ISI:000318174800056
ISSN: 1068-9265
CID: 370042

Screening prior to Breast Cancer Diagnosis: The More Things Change, the More They Stay the Same

Friedman, Erica B; Chun, Jennifer; Schnabel, Freya; Schwartz, Shira; Law, Sidney; Billig, Jessica; Ivanoff, Erin; Moy, Linda; Axelrod, Deborah; Guth, Amber
Purpose. In November 2009, the U.S. Preventative Service Task Force (USPSTF) revised their breast cancer screening guidelines. We evaluated the pattern of screening subsequent to the altered guidelines in a cohort of women. Methods. Our database was queried for the following variables: age, race, method of diagnosis, mass palpability, screening frequency, histology, and stage. Statistical analyses were performed using Pearson's chi-square and Fisher's exact tests. Results. 1112 women were diagnosed with breast cancer from January 2010 to 2012. The median age at diagnosis was 60 years. Most cancers were detected on mammography (61%). The majority of patients had invasive ductal carcinoma (59%), stage 0 (23%), and stage 1 (50%) cancers. The frequency of screening did not change significantly over time (P = 0.30). However, nonregular screeners had an increased risk of being diagnosed with later stage breast cancer (P < 0.001) and were more likely to present with a palpable mass compared to regular screeners (56% versus 21%; P < 0.001). Conclusions. In our study, screening behavior did not significantly change in the years following the USPSTF guidelines. These results suggest that women who are not screened annually are at increased risk of a delay in breast cancer diagnosis, which may impact treatment options and outcomes.
PMCID:3789493
PMID: 24159387
ISSN: 2090-3170
CID: 598542