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32 results on '"Carstens, Julienne L"'

3. Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival

Author

Özdemir, Berna C, Pentcheva-Hoang, Tsvetelina, Carstens, Julienne L, Zheng, Xiaofeng, Wu, Chia-Chin, Simpson, Tyler R, Laklai, Hanane, Sugimoto, Hikaru, Kahlert, Christoph, Novitskiy, Sergey V, De Jesus-Acosta, Ana, Sharma, Padmanee, Heidari, Pedram, Mahmood, Umar, Chin, Lynda, Moses, Harold L, Weaver, Valerie M, Maitra, Anirban, Allison, James P, LeBleu, Valerie S, and Kalluri, Raghu

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Digestive Diseases, Pancreatic Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Carcinoma, Pancreatic Ductal, Disease Models, Animal, Fibroblasts, Fibrosis, Humans, Immune Tolerance, Mice, Mice, Transgenic, Pancreatic Neoplasms, Survival Analysis, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is associated with marked fibrosis and stromal myofibroblasts, but their functional contribution remains unknown. Transgenic mice with the ability to delete αSMA(+) myofibroblasts in pancreatic cancer were generated. Depletion starting at either noninvasive precursor (pancreatic intraepithelial neoplasia) or the PDAC stage led to invasive, undifferentiated tumors with enhanced hypoxia, epithelial-to-mesenchymal transition, and cancer stem cells, with diminished animal survival. In PDAC patients, fewer myofibroblasts in their tumors also correlated with reduced survival. Suppressed immune surveillance with increased CD4(+)Foxp3(+) Tregs was observed in myofibroblast-depleted mouse tumors. Although myofibroblast-depleted tumors did not respond to gemcitabine, anti-CTLA4 immunotherapy reversed disease acceleration and prolonged animal survival. This study underscores the need for caution in targeting carcinoma-associated fibroblasts in PDAC.

Published
2014

4. Novel Pan-RAS Inhibitor ADT-007 Induces Tumor Regression in Mouse Models of GI Cancer

Author

Foote, Jeremy, primary, Mattox, Tyler E, additional, Keeton, Adam B, additional, Smith, Forrest T, additional, Berry, Kristy L, additional, Ward, Antonio B, additional, Yoon, Karina J, additional, Sarvesh, Sujith, additional, Nagaraju, Ganji P, additional, Maxuitenko, Yulia, additional, Chen, Xi, additional, Valiyaveettil,, Jacob, additional, Carstens, Julienne L, additional, Yang, Jennifer, additional, Yang, Jenny, additional, Buchsbaum, Donald J, additional, Zhou, Gang, additional, Nurmmedov, Elmar, additional, Babic, Ivan, additional, Gaponenko, Vadim, additional, Abdelkarim, Hazem, additional, Boyd, Michael R, additional, El-Rayes, Bassel F, additional, and Piazza, Gary A, additional

Published
2023
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5. Abstract LB322: Antitumor activity of 1st-in-class pan-RAS inhibitor ADT-1004 in mouse models of pancreatic ductal adenocarcinoma

Author

Maxuitenko, Yulia Y., primary, Foote, Jeremy B., additional, Keeton, Adam B., additional, Chen, Xi, additional, Berry, Kristy, additional, Fadlalla, Khalda, additional, Valiyaveettil, Jacob, additional, Huang, Chung-Hui, additional, Moore, Austin M., additional, Graff, Emily C., additional, Nagaraju, Ganji P., additional, Carstens, Julienne L., additional, El-Rayes, Bassel F., additional, Buchsbaum, Donald J., additional, and Piazza, Gary A., additional

Published
2023
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6. Data from Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer

Author

McAndrews, Kathleen M., primary, Chen, Yang, primary, Darpolor, J. Kebbeh, primary, Zheng, Xiaofeng, primary, Yang, Sujuan, primary, Carstens, Julienne L., primary, Li, Bingrui, primary, Wang, Huamin, primary, Miyake, Toru, primary, Correa de Sampaio, Pedro, primary, Kirtley, Michelle L., primary, Natale, Mariangela, primary, Wu, Chia-Chin, primary, Sugimoto, Hikaru, primary, LeBleu, Valerie S., primary, and Kalluri, Raghu, primary

Published
2023
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7. Supplementary Data from Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer

Author

McAndrews, Kathleen M., primary, Chen, Yang, primary, Darpolor, J. Kebbeh, primary, Zheng, Xiaofeng, primary, Yang, Sujuan, primary, Carstens, Julienne L., primary, Li, Bingrui, primary, Wang, Huamin, primary, Miyake, Toru, primary, Correa de Sampaio, Pedro, primary, Kirtley, Michelle L., primary, Natale, Mariangela, primary, Wu, Chia-Chin, primary, Sugimoto, Hikaru, primary, LeBleu, Valerie S., primary, and Kalluri, Raghu, primary

Published
2023
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11. Data from FGFR1–WNT–TGF-β Signaling in Prostate Cancer Mouse Models Recapitulates Human Reactive Stroma

Author

Carstens, Julienne L., primary, Shahi, Payam, primary, Van Tsang, Susan, primary, Smith, Billie, primary, Creighton, Chad J., primary, Zhang, Yiqun, primary, Seamans, Amber, primary, Seethammagari, Mamatha, primary, Vedula, Indira, primary, Levitt, Jonathan M., primary, Ittmann, Michael M., primary, Rowley, David R., primary, and Spencer, David M., primary

Published
2023
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12. Supplementary Methods, Figure Legend from FGFR1–WNT–TGF-β Signaling in Prostate Cancer Mouse Models Recapitulates Human Reactive Stroma

Author

Carstens, Julienne L., primary, Shahi, Payam, primary, Van Tsang, Susan, primary, Smith, Billie, primary, Creighton, Chad J., primary, Zhang, Yiqun, primary, Seamans, Amber, primary, Seethammagari, Mamatha, primary, Vedula, Indira, primary, Levitt, Jonathan M., primary, Ittmann, Michael M., primary, Rowley, David R., primary, and Spencer, David M., primary

Published
2023
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13. Supplementary Figures 1 - 8 from FGFR1–WNT–TGF-β Signaling in Prostate Cancer Mouse Models Recapitulates Human Reactive Stroma

Author

Carstens, Julienne L., primary, Shahi, Payam, primary, Van Tsang, Susan, primary, Smith, Billie, primary, Creighton, Chad J., primary, Zhang, Yiqun, primary, Seamans, Amber, primary, Seethammagari, Mamatha, primary, Vedula, Indira, primary, Levitt, Jonathan M., primary, Ittmann, Michael M., primary, Rowley, David R., primary, and Spencer, David M., primary

Published
2023
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14. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer

Author

Zheng, Xiaofeng, Carstens, Julienne L., Kim, Jiha, Scheible, Matthew, Kaye, Judith, Sugimoto, Hikaru, Wu, Chia-Chin, LeBleu, Valerie S., and Kalluri, Raghu

Subjects
Cancer cells -- Analysis, Pancreatic cancer -- Diagnosis -- Prognosis -- Care and treatment, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis despite current best therapies; therefore new treatment strategies are urgently required. Numerous studies have suggested that epithelial-to-mesenchymal transition [...]

Published
2015

15. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis

Author

Lovisa, Sara, LeBleu, Valerie S., Tampe, Bjorn, Sugimoto, Hikaru, Vadnagara, Komal, Carstens, Julienne L., Wu, Chia-Chin, Hagos, Yohannes, Burckhardt, Birgitta C., Pentcheva-Hoang, Tsvetelina, Nischal, Hersharan, Allison, James P., Zeisberg, Michael, and Kalluri, Raghu

Subjects
Fibrosis, Cell differentiation, Biological sciences, Health
Abstract

Kidney fibrosis is marked by an epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs). Here we find that, during renal fibrosis, TECs acquire a partial EMT program during which they remain associated with their basement membrane and express markers of both epithelial and mesenchymal cells. The functional consequence of the EMT program during fibrotic injury is an arrest in the G2 phase of the cell cycle and lower expression of several solute and solvent transporters in TECs. We also found that transgenic expression of either Twist1 (encoding twist family bHLH transcription factor 1, known as Twist) or Snail (encoding snail family zinc finger 1, known as Snail) expression is sufficient to promote prolonged TGF-β1-induced G2 arrest of TECs, limiting the cells' potential for repair and regeneration. In mouse models of experimentally induced renal fibrosis, conditional deletion of Twist1 or Snail in proximal TECs resulted in inhibition of the EMT program and the maintenance of TEC integrity, while also restoring cell proliferation, dedifferentiation-associated repair and regeneration of the kidney parenchyma and attenuating interstitial fibrosis. Thus, inhibition of the EMT program in TECs during chronic renal injury represents a potential anti-fibrosis therapy., Kidney fibrosis is associated with a reduction in the functional renal parenchyma, leading to compromised kidney functions and eventual organ death (1). There is no effective treatment for renal fibrosis [...]

Published
2015
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16. Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer

Author

McAndrews, Kathleen M., primary, Chen, Yang, additional, Darpolor, J. Kebbeh, additional, Zheng, Xiaofeng, additional, Yang, Sujuan, additional, Carstens, Julienne L., additional, Li, Bingrui, additional, Wang, Huamin, additional, Miyake, Toru, additional, Correa de Sampaio, Pedro, additional, Kirtley, Michelle L., additional, Natale, Mariangela, additional, Wu, Chia-Chin, additional, Sugimoto, Hikaru, additional, LeBleu, Valerie S., additional, and Kalluri, Raghu, additional

Published
2022
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20. Abstract A108: Identification of distinct fibroblast populations with unique roles in PDAC progression and tumor immunity

Author

Darpolor, J. Kebbeh, primary, Zheng, Xiaofeng, additional, Yang, Sujuan, additional, McAndrews, Kathleen M., additional, Carstens, Julienne L., additional, Phillips, Patricia E., additional, Sugimoto, Hikaru, additional, De Sampaio, Pedro Correa, additional, Wu, Chia-Chin, additional, LeBleu, Valerie S., additional, and Kalluri, Raghu, additional

Published
2020
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26. Abstract IA15: Functional diversity of the pancreas tumor stroma

Author

LeBleu, Valerie S., primary, Özdemir, Berna C., additional, Pentcheva-Hoang, Tsvetelina, additional, Carstens, Julienne L., additional, Zheng, Xiaofeng, additional, Wu, Chin-Chia, additional, Simpson, Tyler, additional, Laklai, Hanane, additional, Sugimoto, Hikaru, additional, Kahlert, Christoph, additional, Novitskiy, Sergey V., additional, Acosta, Ana DeJesus, additional, Sharma, Padmanee, additional, Heidari, Pedram, additional, Mahmood, Umar, additional, Chin, Lynda, additional, Moses, Harold, additional, Weaver, Valerie, additional, Maitra, Anirban, additional, Allison, James P., additional, and Kalluri, Raghu, additional

Published
2016
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27. Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival

Author

Özdemir, Berna C., primary, Pentcheva-Hoang, Tsvetelina, additional, Carstens, Julienne L., additional, Zheng, Xiaofeng, additional, Wu, Chia-Chin, additional, Simpson, Tyler R., additional, Laklai, Hanane, additional, Sugimoto, Hikaru, additional, Kahlert, Christoph, additional, Novitskiy, Sergey V., additional, De Jesus-Acosta, Ana, additional, Sharma, Padmanee, additional, Heidari, Pedram, additional, Mahmood, Umar, additional, Chin, Lynda, additional, Moses, Harold L., additional, Weaver, Valerie M., additional, Maitra, Anirban, additional, Allison, James P., additional, LeBleu, Valerie S., additional, and Kalluri, Raghu, additional

Published
2015
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28. FGFR1–WNT–TGF-β Signaling in Prostate Cancer Mouse Models Recapitulates Human Reactive Stroma

Author

Carstens, Julienne L., primary, Shahi, Payam, additional, Van Tsang, Susan, additional, Smith, Billie, additional, Creighton, Chad J., additional, Zhang, Yiqun, additional, Seamans, Amber, additional, Seethammagari, Mamatha, additional, Vedula, Indira, additional, Levitt, Jonathan M., additional, Ittmann, Michael M., additional, Rowley, David R., additional, and Spencer, David M., additional

Published
2014
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31. Activation of Wnt Signaling by Chemically Induced Dimerization of LRP5 Disrupts Cellular Homeostasis

Author

Shahi, Payam, primary, Park, Dongsu, additional, Pond, Adam C., additional, Seethammagari, Mamatha, additional, Chiou, Shin-Heng, additional, Cho, Kyucheol, additional, Carstens, Julienne L., additional, Decker, William K., additional, McCrea, Pierre D., additional, Ittmann, Michael M., additional, Rosen, Jeffrey M., additional, and Spencer, David M., additional

Published
2012
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32. A Novel Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth in Mouse Models of GI Cancer.

Author

Foote JB, Mattox TE, Keeton AB, Chen X, Smith F, Berry KL, Holmes T, Wang J, Huang CH, Ward AB, Mitra AK, Ramirez-Alcantara V, Hardy C, Fleten KG, Flatmark K, Yoon KJ, Sarvesh S, Nagaraju GP, Maxuitenko Y, Valiyaveettil J, Carstens JL, Buchsbaum DJ, Yang J, Zhou G, Nurmemmedov E, Babic I, Gaponenko V, Abdelkarim H, Boyd MR, Gorman GS, Manne U, Bae S, El-Rayes BF, and Piazza GA

Abstract

Here, we describe a novel pan-RAS inhibitor, ADT-007, that potently inhibited the growth of RAS mutant cancer cells irrespective of the RAS mutation or isozyme. RAS WT cancer cells with activated RAS from upstream mutations were equally sensitive. Conversely, cells from normal tissues or RAS WT cancer cells harboring downstream BRAF mutations were insensitive. Insensitivity to ADT-007 was attributed to low activated RAS levels and metabolic deactivation by UDP-glucuronosyltransferases expressed in normal cells but repressed in RAS mutant cancer cells. Cellular, biochemical, and biophysical experiments show ADT-007 binds nucleotide-free RAS to block GTP activation of RAS and MAPK/AKT signaling. Local administration of ADT-007 strongly inhibited tumor growth in syngeneic immune-competent and xenogeneic immune-deficient mouse models of colorectal and pancreatic cancer while activating innate and adaptive immunity in the tumor immune microenvironment. Oral administration of ADT-007 prodrug inhibited tumor growth, supporting further development of this novel class of pan-RAS inhibitors for treating RAS-driven cancers., Significance: ADT-007 is a 1 st -in-class pan-RAS inhibitor with ultra-high potency and unique selectivity for cancer cells with mutant or activated RAS capable of circumventing resistance and activating antitumor immunity. Further development of ADT-007 analogs or prodrugs with oral bioavailability as a generalizable monotherapy or combined with immunotherapy is warranted.

Published
2024
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