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  1. Article: Staging of the Axilla in Breast Cancer and the Evolving Role of Axillary Ultrasound.

    Chen, Michael Y / Gillanders, William E

    Breast cancer (Dove Medical Press)

    2021  Volume 13, Page(s) 311–323

    Abstract: Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically. As a result, staging of the axilla has always played a central role in the treatment of breast cancer. Anatomic staging was believed to be important for ... ...

    Abstract Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically. As a result, staging of the axilla has always played a central role in the treatment of breast cancer. Anatomic staging was believed to be important for two reasons: 1) it predicts prognosis and guides medical therapy, and 2) it is a potential therapy for removal of disease in the axilla. This paradigm has now been called into question. Prognostic information is driven increasingly by tumor biology, and trials such as the ACOSOG Z0011 demonstrates removal of axillary disease is not therapeutic. Staging of the axilla has undergone a dramatic de-escalation; however, sentinel lymph node biopsy (SLNB) is still an invasive surgery and represents a large economic burden on the healthcare system. In this review, we outline the changing paradigms of axillary staging in breast cancer from emphasis on anatomic staging to tumor biology, and the evolving role of axillary ultrasound, bringing patients less invasive and more personalized therapy.
    Language English
    Publishing date 2021-05-17
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2520722-2
    ISSN 1179-1314
    ISSN 1179-1314
    DOI 10.2147/BCTT.S273039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Transcription factor C/EBPα is required for the development of Ly6C

    Kim, Sunkyung / Chen, Jing / Ou, Feiya / Liu, Tian-Tian / Jo, Suin / Gillanders, William E / Murphy, Theresa L / Murphy, Kenneth M

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 15, Page(s) e2315659121

    Abstract: Monocytes comprise two major subsets, ... ...

    Abstract Monocytes comprise two major subsets, Ly6C
    MeSH term(s) Animals ; Mice ; Gene Expression Regulation ; Mice, Inbred C57BL ; Monocytes/metabolism ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors ; CEBPA protein, mouse
    Language English
    Publishing date 2024-04-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2315659121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Functional Implications of the Dynamic Regulation of EpCAM during Epithelial-to-Mesenchymal Transition.

    Brown, Taylor C / Sankpal, Narendra V / Gillanders, William E

    Biomolecules

    2021  Volume 11, Issue 7

    Abstract: Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues. EpCAM forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue ... ...

    Abstract Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues. EpCAM forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis. EpCAM is a target of molecular therapies and plays a prominent role in tumor biology. In this review, we focus on the dynamic regulation of EpCAM expression during epithelial-to-mesenchymal transition (EMT) and the functional implications of EpCAM expression on the regulation of EMT. EpCAM is frequently and highly expressed in epithelial cancers, while silenced in mesenchymal cancers. During EMT, EpCAM expression is downregulated by extracellular signal-regulated kinases (ERK) and EMT transcription factors, as well as by regulated intramembrane proteolysis (RIP). The functional impact of EpCAM expression on tumor biology is frequently dependent on the cancer type and predominant oncogenic signaling pathways, suggesting that the role of EpCAM in tumor biology and EMT is multifunctional. Membrane EpCAM is cleaved in cancers and its intracellular domain (EpICD) is transported into the nucleus and binds β-catenin, FHL2, and LEF1. This stimulates gene transcription that promotes growth, cancer stem cell properties, and EMT. EpCAM is also regulated by epidermal growth factor receptor (EGFR) signaling and the EpCAM ectoderm (EpEX) is an EGFR ligand that affects EMT. EpCAM is expressed on circulating tumor and cancer stem cells undergoing EMT and modulates metastases and cancer treatment responses. Future research exploring EpCAM's role in EMT may reveal additional therapeutic opportunities.
    Language English
    Publishing date 2021-06-29
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11070956
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cancer vaccines: shared tumor antigens return to the spotlight.

    Li, Lijin / Goedegebuure, S Peter / Gillanders, William

    Signal transduction and targeted therapy

    2020  Volume 5, Issue 1, Page(s) 251

    MeSH term(s) Antigens, Neoplasm ; Cancer Vaccines ; Humans ; Immunologic Tests ; Melanoma ; RNA
    Chemical Substances Antigens, Neoplasm ; Cancer Vaccines ; RNA (63231-63-0)
    Language English
    Publishing date 2020-10-30
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2886872-9
    ISSN 2059-3635 ; 2095-9907
    ISSN (online) 2059-3635
    ISSN 2095-9907
    DOI 10.1038/s41392-020-00364-8
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  5. Article ; Online: Neoantigen vaccine platforms in clinical development: understanding the future of personalized immunotherapy.

    Supabphol, Suangson / Li, Lijin / Goedegebuure, S Peter / Gillanders, William E

    Expert opinion on investigational drugs

    2021  Volume 30, Issue 5, Page(s) 529–541

    Abstract: Introduction: Derived from genetic alterations, cancer neoantigens are proteins with novel amino acid sequences that can be recognized by the immune system. Recent evidence demonstrates that cancer neoantigens represent important targets of cancer ... ...

    Abstract Introduction: Derived from genetic alterations, cancer neoantigens are proteins with novel amino acid sequences that can be recognized by the immune system. Recent evidence demonstrates that cancer neoantigens represent important targets of cancer immunotherapy. The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and antitumor immunity, while minimizing the potential for autoimmune toxicity. Advances in sequencing technologies, neoantigen prediction ?algorithms,? and other technologies have dramatically improved the ability to identify and prioritize cancer neoantigens. These advances have generated considerable enthusiasm for ?the ?development of neoantigen vaccines. Several neoantigen vaccine platforms are currently being evaluated in early phase clinical trials including the synthetic long peptide (SLP), RNA, dendritic cell (DC), and DNA vaccine platforms.
    Areas covered: In this review, we describe, evaluate the mechanism(s) of action, compare the advantages and disadvantages, and summarize early clinical experience with each vaccine platform. We provide perspectives on the future directions of the neoantigen vaccine field. All data are derived from PubMed and ClinicalTrials search updated in October 2020.
    Expert opinion: Although the initial clinical experience is promising, significant challenges to the success of neoantigen vaccines include limitations in neoantigen identification and the need to successfully target the immunosuppressive tumor microenvironment.
    MeSH term(s) Animals ; Antigens, Neoplasm/immunology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Humans ; Immunotherapy/methods ; Neoplasms/immunology ; Neoplasms/prevention & control ; Precision Medicine ; Tumor Microenvironment/immunology
    Chemical Substances Antigens, Neoplasm ; Cancer Vaccines
    Language English
    Publishing date 2021-03-31
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1182884-5
    ISSN 1744-7658 ; 0967-8298 ; 1354-3784
    ISSN (online) 1744-7658
    ISSN 0967-8298 ; 1354-3784
    DOI 10.1080/13543784.2021.1896702
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3739: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Challenges targeting cancer neoantigens in 2021: a systematic literature review.

    Chen, Ina / Chen, Michael Y / Goedegebuure, S Peter / Gillanders, William E

    Expert review of vaccines

    2021  Volume 20, Issue 7, Page(s) 827–837

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Antigens, Neoplasm ; Cancer Vaccines ; Humans ; Immunotherapy/methods ; Neoplasms ; Tumor Microenvironment
    Chemical Substances Antigens, Neoplasm ; Cancer Vaccines
    Language English
    Publishing date 2021-06-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Systematic Review
    ZDB-ID 2181284-6
    ISSN 1744-8395 ; 1476-0584
    ISSN (online) 1744-8395
    ISSN 1476-0584
    DOI 10.1080/14760584.2021.1935248
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6077: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Cytosolic EpCAM cooperates with H-Ras to regulate epithelial to mesenchymal transition through ZEB1.

    Omar, Fatma A / Brown, Taylor C / Gillanders, William E / Fleming, Timothy P / Smith, Michael A / Bremner, Ross M / Sankpal, Narendra V

    PloS one

    2023  Volume 18, Issue 5, Page(s) e0285707

    Abstract: Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that ... ...

    Abstract Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, we generated a cancer-associated EpCAM mutant (EpCAM-L240A) that is retained in the cytosol compartment. Normal MCF-10A cells were transduced with H-Ras together with EpCAM wild-type (WT) or EpCAM-L240A. WT-EpCAM marginally effected invasion, proliferation, and soft agar growth. EpCAM-L240A, however, markedly altered cells and transformed to mesenchymal phenotype. Ras-EpCAM-L240A expression also promoted expression of EMT factors FRA1, ZEB1 with inflammatory cytokines IL-6, IL-8, and IL1. This altered morphology was reversed using MEK-specific inhibitors and to some extent JNK inhibition. Furthermore, these transformed cells were sensitized to apoptosis using paclitaxel and quercetin, but not other therapies. For the first time, we have demonstrated that EpCAM mutations can cooperate with H-Ras and promote EMT. Collectively, our results highlight future therapeutic opportunities in EpCAM and Ras mutated cancers.
    MeSH term(s) Humans ; Cell Line, Tumor ; Cytosol/metabolism ; Epithelial Cell Adhesion Molecule/genetics ; Epithelial Cell Adhesion Molecule/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Signal Transduction ; Zinc Finger E-box-Binding Homeobox 1/genetics ; Zinc Finger E-box-Binding Homeobox 1/metabolism
    Chemical Substances EPCAM protein, human ; Epithelial Cell Adhesion Molecule ; ZEB1 protein, human ; Zinc Finger E-box-Binding Homeobox 1 ; HRAS protein, human (EC 3.6.5.2)
    Language English
    Publishing date 2023-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0285707
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  8. Article ; Online: Analysis of Preoperative Predictors of Single and Multigland Primary Hyperparathyroidism.

    Frye, C Corbin / Sanka, Sai Anusha / Sullivan, Janessa / Brunt, L Michael / Gillanders, William E / Pandian, T K / Brown, Taylor C

    The Journal of surgical research

    2023  Volume 288, Page(s) 148–156

    Abstract: Introduction: Preoperative differentiation of single-gland (SG) versus multigland (MG) primary hyperparathyroidism (PHPT) can assist with surgical planning, treatment prognostication, and patient counseling. The aim of this study was to identify ... ...

    Abstract Introduction: Preoperative differentiation of single-gland (SG) versus multigland (MG) primary hyperparathyroidism (PHPT) can assist with surgical planning, treatment prognostication, and patient counseling. The aim of this study was to identify preoperative predictors of SG-PHPT.
    Methods: Retrospective analysis of 408 patients with PHPT who underwent parathyroidectomy at a tertiary referral center. Comprehensive preoperative parameters, including demographic, laboratory, clinical, and imaging results were analyzed. Univariate analysis and binary logistic regression identified preoperative predictors of SG-PHPT. Receiver operator curves were used to analyze the predictive values of existing and novel preoperative predictive models.
    Results: Elevated parathyroid hormone (PTH) (99.1 pg/mL in SG versus 93.0 pg/mL in MG), elevated calcium (10.8 mg/dL in SG versus 10.6 mg/dL in MG), lower phosphate levels (2.80 mg/dL in SG versus 2.95 mg/dL in MG), and positive imaging (ultrasound 75.6% in SG versus 56.5% in MG; sestamibi 70.8% in SG versus 45.5% in MG) were significantly associated with SG-PHPT. The Washington University Score (a predictive scoring system made from calcium, PTH, phosphate, ultrasound, and sestamibi) and the Washington University Index ([calcium × PTH]/phosphate) were comparable to previous scoring systems used to predict SG versus MG-PHPT.
    Conclusions: The association of lower phosphate with SG-PHPT is a novel finding. Previously identified predictors of SG-PHPT, including elevated PTH and positive imaging were confirmed. The Washington University Score and Index are comparable to previously described models and can be used to help surgeons predict if a patient may have SG versus MG-PHPT.
    MeSH term(s) Humans ; Calcium ; Hyperparathyroidism, Primary/diagnosis ; Hyperparathyroidism, Primary/surgery ; Parathyroid Hormone ; Retrospective Studies ; Parathyroidectomy/methods ; Radiopharmaceuticals
    Chemical Substances Calcium (SY7Q814VUP) ; Parathyroid Hormone ; Radiopharmaceuticals
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2023.02.011
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 178: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Molecular characteristics of isthmus papillary thyroid cancers: Supporting evidence for unfavorable clinical behavior.

    Smith, Eileen R / Frye, C Corbin / Pandian, T K / Gillanders, William E / Olson, John A / Brown, Taylor C / Jasim, Sina

    American journal of surgery

    2023  Volume 228, Page(s) 146–150

    Abstract: Background: Previous studies demonstrate isthmus thyroid nodules are more likely to be malignant than lobar nodules. Additional data suggest that isthmus papillary thyroid cancers (PTCs) are more aggressive than lobar PTCs. We hypothesize that isthmus ... ...

    Abstract Background: Previous studies demonstrate isthmus thyroid nodules are more likely to be malignant than lobar nodules. Additional data suggest that isthmus papillary thyroid cancers (PTCs) are more aggressive than lobar PTCs. We hypothesize that isthmus PTCs have a more unfavorable molecular profile.
    Methods: The Cancer Genome Atlas (TCGA) database was queried to analyze clinical, mutation and gene expression data of isthmus PTCs compared to non-isthmus PTCs.
    Results: We analyzed characteristics of 472 ​PTCs, including 19 isthmus PTCs. There were no significant differences between isthmus and non-isthmus PTC demographic and clinical variables or the frequency of RAS family, fusion driver, TERT, and tumor suppressor gene mutations. There was a trend towards increased BRAF mutations (68% vs 55%, p ​= ​0.28). A more aggressive gene expression profile was observed in isthmus PTC compared to lobar/multifocal PTC with differences in ERK score (19.4 vs 7.71, p ​< ​0.05) and TDS score (-0.58 vs 0.02, p ​< ​0.05).
    Conclusions: These results provide a possible molecular explanation for the more aggressive behavior reported in isthmus PTCs.
    MeSH term(s) Humans ; Thyroid Cancer, Papillary/genetics ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/pathology ; Carcinoma, Papillary/genetics ; Carcinoma, Papillary/pathology ; Transcriptome ; Proto-Oncogene Proteins B-raf/genetics ; Mutation
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
    Language English
    Publishing date 2023-09-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2953-1
    ISSN 1879-1883 ; 0002-9610
    ISSN (online) 1879-1883
    ISSN 0002-9610
    DOI 10.1016/j.amjsurg.2023.09.005
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    Uk I Zs.42: Show issues Location:
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  10. Article ; Online: IL-6 selectively suppresses cDC1 specification via C/EBPβ.

    Kim, Sunkyung / Chen, Jing / Jo, Suin / Ou, Feiya / Ferris, Stephen T / Liu, Tian-Tian / Ohara, Ray A / Anderson, David A / Wu, Renee / Chen, Michael Y / Gillanders, William E / Gillanders, William E / Murphy, Theresa L / Murphy, Kenneth M

    The Journal of experimental medicine

    2023  Volume 220, Issue 10

    Abstract: Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC ... ...

    Abstract Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPβ binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPβ induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity.
    MeSH term(s) Humans ; Animals ; Mice ; Interleukin-6 ; Binding Sites ; Cytokines ; Dendritic Cells ; Homeostasis
    Chemical Substances Interleukin-6 ; Cytokines
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20221757
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    Ua VI Zs.107: Show issues Location:
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