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  1. Article ; Online: Targeting the type I insulin-like growth factor system for breast cancer therapy.

    Sachdev, Deepali

    Current drug targets

    2010  Volume 11, Issue 9, Page(s) 1121–1132

    Abstract: The insulin-like growth factors (IGFs) acting via the type I IGF receptor (IGF-1R) regulate cancer cell proliferation, survival, metabolism and metastasis. Drugs targeting the IGF-1R are being tested in human clinical trials for cancer therapy and it ... ...

    Abstract The insulin-like growth factors (IGFs) acting via the type I IGF receptor (IGF-1R) regulate cancer cell proliferation, survival, metabolism and metastasis. Drugs targeting the IGF-1R are being tested in human clinical trials for cancer therapy and it seems likely that this class of drugs could be approved soon. Recent data suggests that insulin receptor, which is closely related to IGF-1R, should also be targeted to maximally inhibit the system. Furthermore, biomarkers that will identify patients whose tumors are driven by IGF-1R and biomarkers that allow monitoring or prediction of response are needed. This article reviews the different drugs against IGF-1R that are being tested in and how this receptor pathway can be optimally targeted for cancer therapy with an emphasis on breast cancer therapy.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Female ; Human Growth Hormone/antagonists & inhibitors ; Humans ; Insulin Receptor Substrate Proteins/metabolism ; Insulin-Like Growth Factor I/antagonists & inhibitors ; Insulin-Like Growth Factor I/immunology ; Insulin-Like Growth Factor I/metabolism ; Ligands ; Mice ; Mice, Nude ; Mice, Transgenic ; Molecular Targeted Therapy ; Receptor, IGF Type 1/antagonists & inhibitors ; Receptor, IGF Type 1/metabolism ; Receptor, Insulin/metabolism ; Signal Transduction
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Insulin Receptor Substrate Proteins ; Ligands ; Human Growth Hormone (12629-01-5) ; Insulin-Like Growth Factor I (67763-96-6) ; Receptor, IGF Type 1 (EC 2.7.10.1) ; Receptor, Insulin (EC 2.7.10.1)
    Language English
    Publishing date 2010-06-11
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 2064859-5
    ISSN 1873-5592 ; 1389-4501
    ISSN (online) 1873-5592
    ISSN 1389-4501
    DOI 10.2174/138945010792006816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5578: Show issues Location:
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  2. Article ; Online: Regulation of breast cancer metastasis by IGF signaling.

    Sachdev, Deepali

    Journal of mammary gland biology and neoplasia

    2008  Volume 13, Issue 4, Page(s) 431–441

    Abstract: The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous ... ...

    Abstract The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous clinical trials for cancer including breast cancer. This review discusses the regulation of breast cancer metastasis by IGF-1R. IGF-1R stimulates invasion and survival in anchorage independent conditions. The regulation of metastasis independently of tumor growth by IGF-1R is also discussed. Finally, the impact of this on clinical trial design and outcomes, and the need for biomarkers, other than reduction in tumor size, are discussed in light of the fact that inhibition of metastasis is not measured in conventional clinical trial design.
    MeSH term(s) Animals ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Disease Progression ; Humans ; Neoplasm Metastasis/pathology ; Receptors, Somatomedin/metabolism ; Signal Transduction ; Somatomedins/metabolism
    Chemical Substances Receptors, Somatomedin ; Somatomedins
    Language English
    Publishing date 2008-11-22
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1327345-0
    ISSN 1573-7039 ; 1083-3021
    ISSN (online) 1573-7039
    ISSN 1083-3021
    DOI 10.1007/s10911-008-9105-5
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  3. Article: Drug evaluation: CP-751871, a human antibody against type I insulin-like growth factor receptor for the potential treatment of cancer.

    Sachdev, Deepali

    Current opinion in molecular therapeutics

    2007  Volume 9, Issue 3, Page(s) 299–304

    Abstract: Several phase II trials of CP-751871 are currently underway, including a phase Ib/II [corrected] trial of CP-751871 in combination with paclitaxel and carboplatin in patients with advanced NSCLC, a phase II trial of CP-751871 in combination with ... ...

    Abstract Several phase II trials of CP-751871 are currently underway, including a phase Ib/II [corrected] trial of CP-751871 in combination with paclitaxel and carboplatin in patients with advanced NSCLC, a phase II trial of CP-751871 in combination with docetaxel and prednisone in patients with hormone-refractory prostate cancer, and a phase II trial of CP-751871 in combination with exemestane in hormone receptor positive advanced breast cancer [corrected]
    MeSH term(s) Antibodies/adverse effects ; Antibodies/immunology ; Antibodies/therapeutic use ; Carboplatin/therapeutic use ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Drug Evaluation, Preclinical ; Humans ; Neoplasms/drug therapy ; Paclitaxel/therapeutic use ; Receptors, Somatomedin/immunology
    Chemical Substances Antibodies ; Receptors, Somatomedin ; Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2007-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2022273-7
    ISSN 1464-8431
    ISSN 1464-8431
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5272: Show issues Location:
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  4. Article: Regulation of Breast Cancer Metastasis by IGF Signaling

    Sachdev, Deepali

    Journal of mammary gland biology and neoplasia. 2008 Dec., v. 13, no. 4

    2008  

    Abstract: The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous ... ...

    Abstract The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous clinical trials for cancer including breast cancer. This review discusses the regulation of breast cancer metastasis by IGF-1R. IGF-1R stimulates invasion and survival in anchorage independent conditions. The regulation of metastasis independently of tumor growth by IGF-1R is also discussed. Finally, the impact of this on clinical trial design and outcomes, and the need for biomarkers, other than reduction in tumor size, are discussed in light of the fact that inhibition of metastasis is not measured in conventional clinical trial design.
    Keywords breast neoplasms ; metastasis ; mortality ; antibodies
    Language English
    Dates of publication 2008-12
    Size p. 431-441.
    Publisher Springer US
    Publishing place Boston
    Document type Article
    ZDB-ID 1327345-0
    ISSN 1083-3021
    ISSN 1083-3021
    DOI 10.1007/s10911-008-9105-5
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Discovery of HSPG2 (Perlecan) as a Therapeutic Target in Triple Negative Breast Cancer.

    Kalscheuer, Stephen / Khanna, Vidhi / Kim, Hyunjoon / Li, Sihan / Sachdev, Deepali / DeCarlo, Arthur / Yang, Da / Panyam, Jayanth

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 12492

    Abstract: In recent years, there have been significant advances in the treatment of breast cancer resulting in remarkably high survival rates. However, treatment options for metastatic triple negative breast cancer (TNBC) are quite limited due to a lack of ... ...

    Abstract In recent years, there have been significant advances in the treatment of breast cancer resulting in remarkably high survival rates. However, treatment options for metastatic triple negative breast cancer (TNBC) are quite limited due to a lack of identifiable, unique markers. Using a phage display-based whole cell biopanning procedure, we developed two human antibodies that bind to tumor cells with a metastatic TNBC phenotype. Our studies further identified domain 1 of HSPG2 (perlecan) protein as the cognate cell surface antigen bound by the antibody. Immunohistochemistry studies utilizing patient tissue samples revealed significant cell surface expression of HSPG2 in both primary tumors and metastatic lesions. Further, higher HSPG2 expression correlated with poor survival in TNBC. The affinity-matured antibody inhibited the growth of triple negative MDA-MB-231 tumors to a greater extent in nude mice than in NSG mice, pointing to the potential role of natural killer cell-mediated antibody-dependent cell cytotoxicity. This mechanism of action was confirmed through in vitro assays using mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). These results suggest that HSPG2 is a promising target in metastatic TNBC and HSPG2-targeted antibodies could represent a potentially novel class of targeted therapeutics for TNBC.
    MeSH term(s) Adult ; Animals ; Antibody-Dependent Cell Cytotoxicity/drug effects ; Antineoplastic Agents, Immunological/immunology ; Antineoplastic Agents, Immunological/pharmacology ; Cell Line, Tumor ; Female ; Heparan Sulfate Proteoglycans/genetics ; Heparan Sulfate Proteoglycans/immunology ; Humans ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Proteins/genetics ; Neoplasm Proteins/immunology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/immunology ; Triple Negative Breast Neoplasms/pathology ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents, Immunological ; Heparan Sulfate Proteoglycans ; Neoplasm Proteins ; perlecan (143972-95-6)
    Language English
    Publishing date 2019-08-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-48993-6
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  6. Article ; Online: Discovery of HSPG2 (Perlecan) as a Therapeutic Target in Triple Negative Breast Cancer

    Stephen Kalscheuer / Vidhi Khanna / Hyunjoon Kim / Sihan Li / Deepali Sachdev / Arthur DeCarlo / Da Yang / Jayanth Panyam

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: Abstract In recent years, there have been significant advances in the treatment of breast cancer resulting in remarkably high survival rates. However, treatment options for metastatic triple negative breast cancer (TNBC) are quite limited due to a lack ... ...

    Abstract Abstract In recent years, there have been significant advances in the treatment of breast cancer resulting in remarkably high survival rates. However, treatment options for metastatic triple negative breast cancer (TNBC) are quite limited due to a lack of identifiable, unique markers. Using a phage display-based whole cell biopanning procedure, we developed two human antibodies that bind to tumor cells with a metastatic TNBC phenotype. Our studies further identified domain 1 of HSPG2 (perlecan) protein as the cognate cell surface antigen bound by the antibody. Immunohistochemistry studies utilizing patient tissue samples revealed significant cell surface expression of HSPG2 in both primary tumors and metastatic lesions. Further, higher HSPG2 expression correlated with poor survival in TNBC. The affinity-matured antibody inhibited the growth of triple negative MDA-MB-231 tumors to a greater extent in nude mice than in NSG mice, pointing to the potential role of natural killer cell-mediated antibody-dependent cell cytotoxicity. This mechanism of action was confirmed through in vitro assays using mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). These results suggest that HSPG2 is a promising target in metastatic TNBC and HSPG2-targeted antibodies could represent a potentially novel class of targeted therapeutics for TNBC.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Engaging with plants in an urban environment through street art and design

    Sachdev, Geetanjali

    Plants, people, planet. 2019 July, v. 1, no. 3

    2019  

    Abstract: ... can shine a light on the deep historical and cultural connections that we share with plants. This could be ...

    Abstract Engaging people with botanical street art and design is a good way to draw attention to the botanical world. Here, the importance of plants to people's everyday life in India is highlighted through street art and design. By focusing on the plant motifs present in everyday urban environments, educators can shine a light on the deep historical and cultural connections that we share with plants. This could be a vital tool for those wishing to draw attention to plants in urban settings and highlight their importance for human existence and life on Earth, and as a possible route to counteract plant blindness in urban settings. Summary This article explores plant motifs in street art and design artifacts in India, in order to gain insights toward a pedagogical framework for studying plants in the context of higher education in art and design. The study was carried out as a visual ethnography of the representational use of plants in the public environment, in street art and design artifacts; theoretical implications are drawn from the findings of the ethnographic work for a public pedagogy concerning plants. Across India, street art and craft practices engage with plant representations and plant motifs through diverse materials, techniques, and media. Plant motifs are encountered across personal, professional, and official contexts. Their presence is, in many cases, explained by beliefs in Hinduism, the dominant religion in India. Several historical and culturally meaningful motivations could thereby be established for the use of botanical themes by street artists and craftspeople, which are readily available as a resource for public pedagogy about plants. Plant motifs are common in street art and design artifacts in India. Clear motivations for the public use of these motifs are outlined in the article. The combination of widespread plant motifs and the rich tapestry of motivations for presenting them in the public space offers good scope for a public pedagogy curriculum that highlights the traditional and culturally rich symbolic function of plants in people's lives in this region.
    Keywords anthropology ; blindness ; curriculum ; humans ; people ; religion ; urban areas ; India
    Language English
    Dates of publication 2019-07
    Size p. 271-289.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ISSN 2572-2611
    DOI 10.1002/ppp3.10055
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Disrupting insulin-like growth factor signaling as a potential cancer therapy.

    Sachdev, Deepali / Yee, Douglas

    Molecular cancer therapeutics

    2007  Volume 6, Issue 1, Page(s) 1–12

    Abstract: The type I insulin-like growth factor receptor (IGF-IR) plays multiple roles in several cancers and increased circulating levels of insulin-like growth factor-I (IGF-I) are associated with increased risk of breast, colon, and prostate cancers. Because ... ...

    Abstract The type I insulin-like growth factor receptor (IGF-IR) plays multiple roles in several cancers and increased circulating levels of insulin-like growth factor-I (IGF-I) are associated with increased risk of breast, colon, and prostate cancers. Because IGF-II and insulin signal via the insulin receptor (IR) to stimulate the growth of cancer cells, inhibition of IR might be necessary to totally disrupt the action of IGFs and their receptors. This review describes the well-recognized roles of IGF-IR in driving the malignant phenotype, examines the evidence that perhaps IR should also be targeted to inhibit the effects of the IGF ligands and insulin in cancer, describes the strategies to disrupt IGF signaling in cancer, and highlights some key issues that need to be considered as clinical trials targeting IGF-IR proceed.
    MeSH term(s) Animals ; Clinical Trials as Topic ; Humans ; Neoplasms/therapy ; Receptor, Insulin/metabolism ; Receptors, Somatomedin/antagonists & inhibitors ; Receptors, Somatomedin/metabolism ; Signal Transduction ; Somatomedins/metabolism
    Chemical Substances Receptors, Somatomedin ; Somatomedins ; Receptor, Insulin (EC 2.7.10.1)
    Language English
    Publishing date 2007-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2063563-1
    ISSN 1538-8514 ; 1535-7163
    ISSN (online) 1538-8514
    ISSN 1535-7163
    DOI 10.1158/1535-7163.MCT-06-0080
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5750: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  9. Article: Inhibitors of insulin-like growth factor signaling: a therapeutic approach for breast cancer.

    Sachdev, Deepali / Yee, Douglas

    Journal of mammary gland biology and neoplasia

    2006  Volume 11, Issue 1, Page(s) 27–39

    Abstract: The peptide growth factors IGF-I and IGF-II not only play a role in the development of the mammary gland but are also implicated in breast cancer. Several reagents disrupting IGF signaling have been developed and clinical trials validating IGF signaling ... ...

    Abstract The peptide growth factors IGF-I and IGF-II not only play a role in the development of the mammary gland but are also implicated in breast cancer. Several reagents disrupting IGF signaling have been developed and clinical trials validating IGF signaling as a target in cancer therapy are underway. This review highlights the approaches to inhibiting IGF signaling in breast cancer.
    MeSH term(s) Antibodies, Neoplasm/therapeutic use ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; Breast Neoplasms/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Receptor, IGF Type 1/antagonists & inhibitors ; Receptor, IGF Type 1/immunology ; Receptor, IGF Type 1/metabolism ; Signal Transduction/drug effects
    Chemical Substances Antibodies, Neoplasm ; Antineoplastic Agents ; Protein Kinase Inhibitors ; Receptor, IGF Type 1 (EC 2.7.10.1)
    Language English
    Publishing date 2006-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1327345-0
    ISSN 1083-3021
    ISSN 1083-3021
    DOI 10.1007/s10911-006-9010-8
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  10. Article ; Online: GlioPredictor: a deep learning model for identification of high-risk adult IDH-mutant glioma towards adjuvant treatment planning.

    Zheng, Shuhua / Rammohan, Nikhil / Sita, Timothy / Teo, P Troy / Wu, Yilin / Lesniak, Maciej / Sachdev, Sean / Thomas, Tarita O

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 2126

    Abstract: Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a ... ...

    Abstract Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a combination of molecular markers that could be used to identify patients who may have a greater need for adjuvant radiation therapy machine learning technology. 507 WHO Grade 2 and 3 glioma cases from The Cancer Genome Atlas, and 1309 cases from AACR GENIE v13.0 datasets were studied for genetic disparities between IDH1-wildtype and IDH1-mutant cohorts, and between different age groups. Genetic features such as mutations and copy number variations (CNVs) correlated with IDH1 mutation status were selected as potential inputs to train artificial neural networks (ANNs) to predict IDH1 mutation status. Grade 2 and 3 glioma cases from the Memorial Sloan Kettering dataset (n = 404) and Grade 3 glioma cases with subtotal resection (STR) from Northwestern University (NU) (n = 21) were used to further evaluate the best performing ANN model as independent datasets. IDH1 mutation is associated with decreased CNVs of EGFR (21% vs. 3%), CDKN2A (20% vs. 6%), PTEN (14% vs. 1.7%), and increased percentage of mutations for TP53 (15% vs. 63%), and ATRX (10% vs. 54%), which were all statistically significant (p < 0.001). Age > 40 was unable to identify high-risk IDH1-mutant with early progression. A glioma early progression risk prediction (GlioPredictor) score generated from the best performing ANN model (6/6/6/6/2/1) with 6 inputs, including CNVs of EGFR, PTEN and CDKN2A, mutation status of TP53 and ATRX, patient's age can predict IDH1 mutation status with over 90% accuracy. The GlioPredictor score identified a subgroup of high-risk IDH1-mutant in TCGA and NU datasets with early disease progression (p = 0.0019, 0.0238, respectively). The GlioPredictor that integrates age at diagnosis, CNVs of EGFR, CDKN2A, PTEN and mutation status of TP53, and ATRX can identify a small cohort of IDH-mutant with high risk of early progression. The current version of GlioPredictor mainly incorporated clinically often tested genetic biomarkers. Considering complexity of clinical and genetic features that correlate with glioma progression, future derivatives of GlioPredictor incorporating more inputs can be a potential supplement for adjuvant radiotherapy patient selection of IDH-mutant glioma patients.
    MeSH term(s) Adult ; Humans ; Isocitrate Dehydrogenase/genetics ; DNA Copy Number Variations ; Deep Learning ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Glioma/genetics ; Glioma/therapy ; Cyclin-Dependent Kinase Inhibitor Proteins ; ErbB Receptors/genetics
    Chemical Substances Isocitrate Dehydrogenase (EC 1.1.1.41) ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Cyclin-Dependent Kinase Inhibitor Proteins ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-51765-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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