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2. iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells

Author

Bouguenina, Habib, Nicolaou, Stephanos, Le Bihan, Yann-Vaï, Bowling, Elizabeth A., Calderon, Cheyenne, Caldwell, John J., Harrington, Brinley, Hayes, Angela, McAndrew, P. Craig, Mitsopoulos, Costas, Sialana, Fernando Jr., Scarpino, Andrea, Stubbs, Mark, Thapaliya, Arjun, Tyagi, Siddhartha, Wang, Hannah Z., Wood, Francesca, Burke, Rosemary, Raynaud, Florence, Choudhary, Jyoti, van Montfort, Rob L.M., Sadok, Amine, Westbrook, Thomas F., Collins, Ian, and Chopra, Rajesh

Published
2023
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3. iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells

Author

Bouguenina, Habib, primary, Nicolaou, Stephanos, additional, Bihan, Yann-Vaï Le, additional, Bowling, Elizabeth A., additional, Calderon, Cheyenne, additional, Caldwell, John J., additional, Harrington, Brinley, additional, Hayes, Angela, additional, McAndrew, P. Craig, additional, Mitsopoulos, Costas, additional, Sialana, Fernando Jr., additional, Scarpino, Andrea, additional, Stubbs, Mark, additional, Thapaliya, Arjun, additional, Tyagi, Siddhartha, additional, Wang, Hannah Z., additional, Wood, Francesca, additional, Burke, Rosemary, additional, Raynaud, Florence, additional, Choudhary, Jyoti, additional, van Montfort, Rob L.M., additional, Sadok, Amine, additional, Westbrook, Thomas F., additional, Collins, Ian, additional, and Chopra, Rajesh, additional

Published
2024
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5. Signs and lines in lung ultrasound

Author

Bhoil Rohit, Ahluwalia Ajay, Chopra Rajesh, Surya Mukesh, and Bhoil Sabina

Subjects
sonography, emergency ultrasound, pocus, blue protocol, Medicine (General), R5-920, Medical technology, R855-855.5
Abstract

Point-of-care ultrasound has become firmly established in acute and critical care settings, and is now increasingly being used as an important tool in the assessment of the lungs. In this article, we briefly describe the technique of lung ultrasound and the various lines and signs commonly encountered during sonography of the lung, namely the normally visualised A- and T-lines and the bat sign, sliding sign (power slide sign on colour Doppler), sea-shore sign, curtain sign, and the lung pulse. We have also described signs seen in various pathological conditions like B-lines seen in cases of increased lung density; the quad sign, sinusoid sign, thoracic spine sign, plankton sign and the jelly fish sign seen in pleural effusion; the stratosphere sign and the lung point sign seen in pneumothorax; the shred/fractal sign and tissue-like sign in consolidation, and the double lung point sign seen in transient tachypnoea of the newborn. With adequate and appropriate training, lung ultrasound can be effectively utilised as a point-of-care investigation.

Published
2021
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8. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma

Author

Wei, Wei, Shin, Young Shik, Xue, Min, Matsutani, Tomoo, Masui, Kenta, Yang, Huijun, Ikegami, Shiro, Gu, Yuchao, Herrmann, Ken, Johnson, Dazy, Ding, Xiangming, Hwang, Kiwook, Kim, Jungwoo, Zhou, Jian, Su, Yapeng, Li, Xinmin, Bonetti, Bruno, Chopra, Rajesh, James, C David, Cavenee, Webster K, Cloughesy, Timothy F, Mischel, Paul S, Heath, James R, and Gini, Beatrice

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Cancer, Neurosciences, Biotechnology, Rare Diseases, Brain Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Adaptation, Physiological, Animals, Antineoplastic Combined Chemotherapy Protocols, Brain Neoplasms, Butadienes, Dasatinib, Drug Resistance, Neoplasm, Drug Synergism, ErbB Receptors, Gene Expression Profiling, Genes, erbB-1, Glioblastoma, Humans, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Mice, Models, Biological, Molecular Targeted Therapy, Multiprotein Complexes, Mutation, Neoplasm Proteins, Nitriles, Phosphoproteins, Protein Kinase Inhibitors, Proteomics, Pyrazines, Selection, Genetic, Signal Transduction, Single-Cell Analysis, TOR Serine-Threonine Kinases, Xenograft Model Antitumor Assays, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations.

Published
2016

14. A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity

Author

Bouguenina, Habib, primary, Scarpino, Andrea, additional, O'Hanlon, Jack A., additional, Warne, Justin, additional, Wang, Hannah Z., additional, Wah Hak, Laura Chan, additional, Sadok, Amine, additional, McAndrew, P. Craig, additional, Stubbs, Mark, additional, Pierrat, Olivier A., additional, Hahner, Tamas, additional, Cabry, Marc P., additional, Le Bihan, Yann‐Vaï, additional, Mitsopoulos, Costas, additional, Sialana, Fernando J., additional, Roumeliotis, Theodoros I., additional, Burke, Rosemary, additional, van Montfort, Rob L. M., additional, Choudhari, Jyoti, additional, Chopra, Rajesh, additional, Caldwell, John J., additional, and Collins, Ian, additional

Published
2023
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15. Challenges to curing primary brain tumours

Author

Aldape, Kenneth, Brindle, Kevin M., Chesler, Louis, Chopra, Rajesh, Gajjar, Amar, Gilbert, Mark R., Gottardo, Nicholas, Gutmann, David H., Hargrave, Darren, Holland, Eric C., Jones, David T. W., Joyce, Johanna A., Kearns, Pamela, Kieran, Mark W., Mellinghoff, Ingo K., Merchant, Melinda, Pfister, Stefan M., Pollard, Steven M., Ramaswamy, Vijay, Rich, Jeremy N., Robinson, Giles W., Rowitch, David H., Sampson, John H., Taylor, Michael D., Workman, Paul, and Gilbertson, Richard J.

Published
2019
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17. A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity.

Author

Bouguenina, Habib, Scarpino, Andrea, O'Hanlon, Jack A., Warne, Justin, Wang, Hannah Z., Wah Hak, Laura Chan, Sadok, Amine, McAndrew, P. Craig, Stubbs, Mark, Pierrat, Olivier A., Hahner, Tamas, Cabry, Marc P., Le Bihan, Yann‐Vaï, Mitsopoulos, Costas, Sialana, Fernando J., Roumeliotis, Theodoros I., Burke, Rosemary, van Montfort, Rob L. M., Choudhari, Jyoti, and Chopra, Rajesh

Published
2023
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21. Supplementary Figure 5 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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22. Supplementary Figure 4 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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23. Supplementary Figure 1 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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24. Supplementary Figure Legend from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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25. Supplementary Figure 3 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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26. Data from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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27. Supplementary Figure 2 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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29. Supplementary Figure 6 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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30. Supplementary Figure 7 from The mTOR Kinase Inhibitors, CC214-1 and CC214-2, Preferentially Block the Growth of EGFRvIII-Activated Glioblastomas

Author

Gini, Beatrice, primary, Zanca, Ciro, primary, Guo, Deliang, primary, Matsutani, Tomoo, primary, Masui, Kenta, primary, Ikegami, Shiro, primary, Yang, Huijun, primary, Nathanson, David, primary, Villa, Genaro R., primary, Shackelford, David, primary, Zhu, Shaojun, primary, Tanaka, Kazuhiro, primary, Babic, Ivan, primary, Akhavan, David, primary, Lin, Kelly, primary, Assuncao, Alvaro, primary, Gu, Yuchao, primary, Bonetti, Bruno, primary, Mortensen, Deborah S., primary, Xu, Shuichan, primary, Raymon, Heather K., primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, James, C. David, primary, Kroemer, Guido, primary, Heath, James R., primary, Hege, Kristen, primary, Chopra, Rajesh, primary, Cloughesy, Timothy F., primary, and Mischel, Paul S., primary

Published
2023
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31. The expression and regulation of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR)

Author

Chopra, Rajesh

Subjects
572.8, Genetics
Abstract

The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) consists of a specific α chain which binds ligand with low affinity and a β chain which confers high affinity binding. The aim of this thesis was to investigate the expression and regulation of the GM-CSFR. RNase protection assays were developed in order to detect the low abundance mRNA species. The GM-CSFRa mRNA expression was determined to be in the pg range and the β mRNA expression at least one log lower. GM- CSFRa mRNA expression was demonstrated in a number of haemopoietic cell lines and the expression of GM-CSFRa mRNA was consistently higher than that of GM-CSFRα mRNA, which is in keeping with the receptor protein expression. RNase protection assays of GM-CSFRα yielded extra bands in addition to the expected mRNA transcript. Characterisation studies, using RT-PCR, established the existence of at least two additional mRNA transcripts involving alternative splicing of the 5' untranslated region of the GM-CSFRa chain. Sequencing demonstrated that these isoforms were the result of a deletion of 24 nucleotides at the 3' end of exon 2 (exon 2b deleted isoform) and complete deletion of exon 2 (exon 2 deleted isoform). These isoforms were detected in primary haemopoietic cells, blasts from patients with acute myeloid leukaemia and malignant cell lines. Together the isoforms were more highly expressed than the full length sequence. Translation of constructs corresponding to the exon 2 deleted isoforms was assessed using an in-vitro reticulocyte lysate system. Deletion of exon 2 resulted in a significantly lower in vitro translation of the receptor protein compared to the full length sequence, whilst deletion of exon 2b results in higher translation of the a chain protein. These in vitro studies therefore identified putative regulatory sequences that may modulate translation of the GM-CSFRα chain. In order to investigate the underlying mechanisms by which the receptor expression is regulated, GM-CSFR binding and mRNA expression were investigated using two model systems: TF-1 cells undergoing down and up- regulation of surface receptors; and HL-60 cells undergoing DMSO-induced differentiation. The half-life of the GM-CSFR protein in TF-1 cells growing in steady state conditions in the presence of Epo and the translation inhibitor cycloheximide, was approximately 4 hours, which would indicate a constant nonligand mediated turnover of cell surface receptor protein. Incubation of the TF-1 cells in the presence of the transcription inhibitor actinomycin-D indicated that the half-life of the GM-CSFRα mRNA was between 1-3 hours and that of the GM-CSFR α mRNA greater than 8 hours. The cell surface expression of the specific GM-CSFRα and β chains and mRNA levels however, did not change in the presence of actinomycin D, implying post-transcriptional regulation of the GM- CSFR expression. In order to further clarify the nature of this post-transcriptional regulation, cell surface receptor expression in cells undergoing up-regulation of their receptor was measured. Up-regulation was inhibited in the presence of cycloheximide, but not by the lysosomotropic agent ammonium chloride, suggesting that new protein synthesis, rather than receptor recycling, is important when GM-CSFR expression is dynamically modulated. Uninduced HL-60 cells express low numbers of both low and high affinity receptors and on induction with DMSO for 5 days, the receptor numbers increased and both the GM-CSFRα and β mRNA levels showed a co-ordinate increase. This implies transcriptional regulation of the GM-CSFRα and β chains during differentiation. The different mechanisms described for GM-CSFR regulation may explain at least in part, how GM-CSF can act through its receptor to modulate long term differentiation events and at the same time augment mature cell function where the control mechanisms take place over a time course of minutes and hours.

Published
1996

34. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL

Author

Hagner, Patrick R., Man, Hon-Wah, Fontanillo, Celia, Wang, Maria, Couto, Suzana, Breider, Mike, Bjorklund, Chad, Havens, Courtney G., Lu, Gang, Rychak, Emily, Raymon, Heather, Narla, Rama Krishna, Barnes, Leo, Khambatta, Gody, Chiu, Hsiling, Kosek, Jolanta, Kang, Jian, Amantangelo, Michael D., Waldman, Michelle, Lopez-Girona, Antonia, Cai, Ti, Pourdehnad, Michael, Trotter, Matthew, Daniel, Thomas O., Schafer, Peter H., Klippel, Anke, Thakurta, Anjan, Chopra, Rajesh, and Gandhi, Anita K.

Published
2015
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36. JNK inhibition reduces lung remodeling and pulmonary fibrotic systemic markers

Author

van der Velden, Jos L. J., Ye, Ying, Nolin, James D., Hoffman, Sidra M., Chapman, David G., Lahue, Karolyn G., Abdalla, Sarah, Chen, Peng, Liu, Yong, Bennett, Brydon, Khalil, Nasreen, Sutherland, Donna, Smith, William, Horan, Gerald, Assaf, Mahmoud, Horowitz, Zebulun, Chopra, Rajesh, Stevens, Randall M., Palmisano, Maria, Janssen-Heininger, Yvonne M. W., and Schafer, Peter H.

Published
2016
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37. 1316 A novel class of T cell-activating antibody that selectively targets the TCR b chain to promote antitumor activity through activation and expansion of a novel, polyclonal effector memory T cell subset

Author

Bayliffe, Andy, primary, Su, Zhen, additional, Wherry, John, additional, Hsu, Jonathan, additional, Katraggada, Madan, additional, Moisan, Jacques, additional, Guntas, Gurkan, additional, Srinivasan, Karunya, additional, Lowry, Jessica, additional, Chopra, Rajesh, additional, Servattalab, Roya, additional, Huang, Wei, additional, and Tang, Jian, additional

Published
2022
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38. 1337 Preclinical evaluation of STAR0602, a novel, first-in-class anti-TCR Vb targeted bispecific antibody with potent anti-tumor activity for PD-1 refractory solid tumors

Author

Su, Zhen, primary, Gulley, James, additional, Schlom, Jeffrey, additional, Siu, Lillian, additional, Sullivan, Ryan, additional, John Wherry, E, additional, Liu, Ke, additional, Donahue, Renee, additional, Katraggada, Madan, additional, Chopra, Rajesh, additional, Moisan, Jacques, additional, Hsu, Jonathan, additional, and Tsai, Yo-Ting, additional

Published
2022
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41. Reply to ‘Assembling the brain trust: the multidisciplinary imperative in neuro-oncology’

Author

Aldape, Kenneth, Brindle, Kevin M., Chesler, Louis, Chopra, Rajesh, Gajjar, Amar, Gilbert, Mark R., Gottardo, Nicholas, Gutmann, David H., Hargrave, Darren, Holland, Eric C., Jones, David T. W., Joyce, Johanna A., Kearns, Pamela, Kieran, Mark W., Mellinghoff, Ingo K., Merchant, Melinda, Pfister, Stefan M., Pollard, Steven M., Ramaswamy, Vijay, Rich, Jeremy N., Robinson, Giles W., Rowitch, David H., Sampson, John H., Taylor, Michael D., Workman, Paul, and Gilbertson, Richard J.

Published
2019
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42. Role of ultrasound and electro-diagnostic studies in the diagnosis of carpal tunnel syndrome: A comparative study

Author

Jaiman Ashish, Benthungo N. Tungoe, Rajesh Kumar Chopra, Yatish Agarwal, Chopra Rajesh Kumar, Agarwal Yatish, Ashish Jaiman, and N Tungoe Benthungo

Subjects
030222 orthopedics, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cross-sectional study, Ultrasound, Physical examination, Gold standard (test), medicine.disease, Median nerve, nervous system diseases, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Medicine, Upper limb, Orthopedics and Sports Medicine, Surgery, Carpal tunnel, 030212 general & internal medicine, Radiology, business, Carpal tunnel syndrome
Abstract

BACKGROUND: The current gold standard for the diagnosis of Carpal tunnel syndrome (CTS) is a topic of debate. Nerve conduction studies (NCS) traditionally have been used as the confirmatory test; however, ultrasound (USG) has garnered interest as an alternative diagnostic test for CTS. Ultrasound measurement of the cross sectional area of the median nerve at the carpal tunnel has been proposed as an alternative for confirmation of CTS. AIM: The aim of the study was to compare the sensitivity and specificity between Ultrasound and Electro-diagnostic Studies in the diagnosis of Carpal Tunnel Syndrome with reference to a validated clinical diagnostic tool i.e. CTS- 6; that combines findings from the history and physical examination. MATERIALS AND METHODS: 40 (20 Cases and 20 controls) adult patients and adolescents of both sexes with complain of pain and paraesthesia in upper limb were included in this cross sectional study. All patients were evaluated using CTS-6 clinical diagnostic tool. Those patients with CTS score12 were considered as positive diagnosis for Carpal Tunnel Syndrome (cases) (Main group). Those patients with CTS Score12 were taken as Controls. Ultrasound and Electro-diagnostic Studies were performed by individuals blinded to the results of the CTS-6 and ultrasound examination. RESULTS: We found that USG have sensitivity of 90%, specificity of 85%, and positive predictive value of 85.71% and negative predictive value of 89.47%. Whereas NCS have sensitivity of 85%, specificity of 80%, positive predictive value of 80.95% and negative predictive value of 84.21%. CONCLUSION: Using CTS-6 clinical tool as a standard reference, the sensitivity and specificity of USG is more than that of NCS.

Published
2021

44. Missed posterior shoulder dislocation with malunited proximal humerus fracture

Author

Kumar Sunil, Chopra Rajesh Kumar, Kashyap Abhishek, and Arora Sumit

Subjects
Medicine (General), R5-920
Abstract

【Abstract】Posterior dislocation of the shoulder may be missed or neglected at initial presentation especially in developing countries. We present a case of 40-year-old In- dian man who had 3-month missed posterior dislocation of the right shoulder along with malunited fracture of the ana- tomical neck of the humerus. Open reduction and stabiliza- tion with modified McLaughlin procedure was performed. Rotational osteotomy of proximal humerus had to be per- formed as supplementary procedure to keep the humeral head stable in glenoid cavity during functional range of movements. The patient had excellent result of the shoulder at 3 years follow-up. Key words: Shoulder dislocation; Humerus; Osteotomy

Published
2013

46. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS

Author

Kronke, Jan, Fink, Emma C., Hollenbach, Paul W., MacBeth, Kyle J., Hurst, Slater N., Udeshi, Namrata D., Chamberlain, Philip P., Mani, D.R., Man, Hon Wah, Gandhi, Anita K., Svinkina, Tanya, Schneider, Rebekka K., McConkey, Marie, Jaras, Marcus, Griffiths, Elizabeth, Wetzler, Meir, Bullinger, Lars, Cathers, Brian E., Carr, Steven A., Chopra, Rajesh, and Ebert, Benjamin L.

Subjects
Ubiquitin-proteasome system -- Health aspects, Myelodysplastic syndromes -- Drug therapy, Phosphotransferases -- Health aspects, Casein -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1α) by the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as [CRL4.sup.CRBN]), resulting in CK1α degradation. CK1α is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for the therapeutic window of lenalidomide in del(5q) MDS. We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1α. We further demonstrate that minor side chain modifications in thalidomide and a novel analogue, CC-122, can modulate the spectrum of substrates targeted by [CRL4.sup.CRBN]. These findings have implications for the clinical activity of lenalidomide and related compounds, and demonstrate the therapeutic potential of novel modulators of E3 ubiquitin ligases., The immunomodulatory (IMiD) agents lenalidomide, thalidomide, and pomalidomide are the first drugs identified that promote the ubiquitination and degradation of specific substrates by an E3 ubiquitin ligase. These compounds bind [...]

Published
2015
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49. Abstract LBA004: Identification of GSPT1-directed molecular glue degrader (MGD) for the treatment of Myc-driven breast cancer

Author

Gavory, Gerald, primary, Fasching, Bernhard, additional, Bonenfant, Debora, additional, Sadok, Amine, additional, Singh, Ambika, additional, Schillo, Martin, additional, Massafra, Vittoria, additional, d’Alessandro, Anne-Cecile, additional, Castle, John, additional, Ghandi, Mahmoud, additional, Chicas, Agustin, additional, Delobel, Frederic, additional, Flohr, Alexander, additional, Ottaviani, Giorgio, additional, Ryckmans, Thomas, additional, Laine, Anne-Laure, additional, Eidam, Oliv, additional, Wang, Hannah, additional, Bernett, Ilona, additional, Chan, Laura, additional, Gorrini, Chiara, additional, Roumiliotis, Theo, additional, Choudhary, Jyoti, additional, LeBihan, Yann-Vai, additional, Cabry, Marc, additional, Stubbs, Mark, additional, Burke, Rosemary, additional, Van Montfort, Rob, additional, Caldwell, John, additional, Chopra, Rajesh, additional, Collins, Ian, additional, and Buonamici, Silvia, additional

Published
2021
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50. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis

Author

Suragani, Rajasekhar N V S, Cadena, Samuel M., Cawley, Sharon M., Sako, Dianne, Mitchell, Dianne, Li, Robert, Davies, Monique V., Alexander, Mark J., Devine, Matthew, Loveday, Kenneth S., Underwood, Kathryn W., Grinberg, Asya V., Quisel, John D., Chopra, Rajesh, Pearsall, R Scott, Seehra, Jasbir, and Kumar, Ravindra

Subjects
Anemia -- Genetic aspects -- Care and treatment -- Research, Erythropoiesis -- Physiological aspects -- Genetic aspects -- Research, Transforming growth factors -- Physiological aspects -- Genetic aspects -- Research, Biological sciences, Health
Abstract

Erythropoietin (EPO) stimulates proliferation of early-stage erythrocyte precursors and is widely used for the treatment of chronic anemia. However, several types of EPO-resistant anemia are characterized by defects in late-stage [...]

Published
2014

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