Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

Baraban, Ezra; Sadigh, Sam; Rosenbaum, Jason N.; Arnam, John Van; Bogusz, Agata M.; Mehr, Chelsea R.; Bagg, Adam

doi:10.1111/bjh.16006

Cited by 35 publications

(24 citation statements)

References 27 publications

(29 reference statements)

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“…In TE-1 cells, cyclin B1, CDK1 and Cdc25c were decreased. However, no notable change was observed for cyclin D1, which is a regulator that drives cells from the G1 phase to S phase (25). All these data suggest that nimotuzumab induces cell cycle arrest at the G2 phase to inhibit cell proliferation.…”

Section: Nimotuzumab Arrests the Escc Cell Cycle At The G2 Phasementioning

confidence: 86%

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma

Guan

Jiang

et al. 2020

Int J Oncol

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Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)-targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR-targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE-1, with or without nimotuzumab, were first evaluated by CCK-8 assay. Colony formation and apoptosis were used to measure anti-proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P<0.001 for 0 Gy pre-irradiation, P=0.005 for 20 Gy pre-irradiation, P=0.005 for 10 Gy pre-irradiation). These results suggest that nimotuzumab combined with radiation may be an effective means to control recurrent esophageal squamous cell carcinoma with EGFR overexpression.

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Section: Nimotuzumab Arrests the Escc Cell Cycle At The G2 Phasementioning

confidence: 86%

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma

Guan

Jiang

et al. 2020

Int J Oncol

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“…Our molecular findings offer support for such classification, as HS, LCS, and IDCS harbor similar alterations with recurrent alterations in the MAPK pathway and frequent CDKN2A and TP53 mutations. Although MAPK pathway alterations are prevalent in M group histiocytoses and other more indolent histiocytic entities (including Langerhans cell histiocytosis, Erdheim‐Chester disease, and Rosai‐Dorfman disease/sinus histiocytosis with massive lymphadenopathy) [ 4 , 33 , 34 , 35 , 36 , 37 , 38 ], mutations in CDKN2A and TP53 appear rare in the latter group [ 34 ] and may help account for the more aggressive clinicopathologic features in M group histiocytoses.…”

Section: Discussionmentioning

confidence: 99%

Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma

et al. 2021

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Background. Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking. Methods. Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer-related genes. Results. Among the entire cohort of 102 patients, CDKN2A mutations were most frequent across subtypes and made up 32% of cases, followed by TP53 mutations (22%). Mitogen-activated protein kinase (MAPK) pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCS (72% vs. 0%; p < .0001). In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytoses (61% vs. 12%; p < .0001). Tumor mutational burden was significantly higher in M group histiocytoses as compared with FDCSs (median 4.0/Mb vs. 2.4/ Mb; p = .012). We also describe a pediatric patient with recurrent secondary histiocytic sarcoma treated with targeted therapy and interrogated by molecular analysis to identify mechanisms of therapeutic resistance. Conclusion. A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. Our findings highlight the potential value of molecular testing to enable precise tumor classification, identify candidate oncogenic drivers, and define personalized therapeutic options for patients with these aggressive tumors.

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“…121 Cyclin D1 expression by the abnormal histiocytes, and increased IgG4-positive plasma cells in the background inflammatory infiltrate, may also be found. 129,130 Unlike LCH and ECD, BRAF V600E activating mutations are not commonly seen in patients with RDD. 3,12,121 KRAS, MAP21K, ARAF, and NRAS mutations have been found in patients with RDD.…”

Section: Diagnosis Of Rddmentioning

confidence: 99%

Histiocytic Neoplasms, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Go¹,

Jacobsen

Baiocchi

et al. 2021

Journal of the National Comprehensive Cancer Network

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Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation (“watch and wait”) may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.

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Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

Cited by 35 publications

References 27 publications

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma

Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma

Histiocytic Neoplasms, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

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