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Article: Ovarian Cancer Targeted Theranostics.

Nimmagadda, Sridhar / Penet, Marie-France

2020 Volume 9, Page(s) 1537

Abstract: Ovarian cancer is a leading cause of death from gynecological malignancies. Although the prognosis is quite favorable if detected at an early stage, the vast majority of cases are diagnosed at an advanced stage, when 5-year survival rates are only 30-40%. ...

Abstract	Ovarian cancer is a leading cause of death from gynecological malignancies. Although the prognosis is quite favorable if detected at an early stage, the vast majority of cases are diagnosed at an advanced stage, when 5-year survival rates are only 30-40%. Most recurrent ovarian tumors are resistant to traditional therapies underscoring the need for new therapeutic options. Theranostic agents, that combine diagnostic and therapeutic capabilities, are being explored to better detect, diagnose and treat ovarian cancer. To minimize morbidity, improve survival rates, and eventually cure patients, new strategies are needed for early detection and for delivering specifically anticancer therapies to tumor sites. In this review we will discuss various molecular imaging modalities and targets that can be used for imaging, therapeutic and theranostic agent development for improved diagnosis and treatment of ovarian cancer.
Language	English
Publishing date	2020-01-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.01537
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Article: Water and Collagen Content Are High in Pancreatic Cancer: Implications for Quantitative Metabolic Imaging.

Penet, Marie-France / Kakkad, Samata / Wildes, Flonné / Bhujwalla, Zaver M

Frontiers in oncology

2021 Volume 10, Page(s) 599204

Abstract: In magnetic resonance metabolic imaging, signal from the water content is frequently used for normalization to derive quantitative or semi-quantitative values of ... ...

Abstract	In magnetic resonance metabolic imaging, signal from the water content is frequently used for normalization to derive quantitative or semi-quantitative values of metabolites
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.599204
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Article: Phototheranostics of Splenic Myeloid-Derived Suppressor Cells and Its Impact on Spleen Metabolism in Tumor-Bearing Mice.

Barnett, James D / Jin, Jiefu / Penet, Marie-France / Kobayashi, Hisataka / Bhujwalla, Zaver M

Cancers

2022 Volume 14, Issue 15

Abstract: 1) Background: MDSCs play an active role in the immune surveillance escape of cancer cells. Because MDSCs in mice are ... ...

Abstract	(1) Background: MDSCs play an active role in the immune surveillance escape of cancer cells. Because MDSCs in mice are CD11b
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14153578
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Article ; Online: Twist alters the breast tumor microenvironment via choline kinase to facilitate an aggressive phenotype.

Vesuna, Farhad / Penet, Marie-France / Mori, Noriko / Bhujwalla, Zaver M / Raman, Venu

Molecular and cellular biochemistry

2022 Volume 478, Issue 4, Page(s) 939–948

Abstract: Twist (TWIST1) is a gene required for cell fate specification in embryos and its expression in mammary epithelium can initiate tumorigenesis through the epithelial-mesenchymal transition. To identify downstream target genes of Twist in breast cancer, we ... ...

Abstract	Twist (TWIST1) is a gene required for cell fate specification in embryos and its expression in mammary epithelium can initiate tumorigenesis through the epithelial-mesenchymal transition. To identify downstream target genes of Twist in breast cancer, we performed microarray analysis on the transgenic breast cancer cell line, MCF-7/Twist. One of the targets identified was choline kinase whose upregulation resulted in increased cellular phosphocholine and total choline containing compounds-a characteristic observed in highly aggressive metastatic cancers. To study the interactions between Twist, choline kinase, and their effect on the microenvironment, we used
MeSH term(s)	Cell Line, Tumor ; Choline/metabolism ; Choline Kinase/genetics ; Choline Kinase/metabolism ; Phenotype ; Phosphorylcholine/metabolism ; Tumor Microenvironment ; Twist-Related Protein 1/genetics ; Twist-Related Protein 1/metabolism
Chemical Substances	Choline (N91BDP6H0X) ; Choline Kinase (EC 2.7.1.32) ; Phosphorylcholine (107-73-3) ; Twist-Related Protein 1 ; TWIST1 protein, human
Language	English
Publishing date	2022-09-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-022-04555-5
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Zs.A 892: 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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Article ; Online: Cancer insights from magnetic resonance spectroscopy of cells and excised tumors.

Penet, Marie-France / Sharma, Raj Kumar / Bharti, Santosh / Mori, Noriko / Artemov, Dmitri / Bhujwalla, Zaver M

NMR in biomedicine

2022 Volume 36, Issue 4, Page(s) e4724

Abstract: Multinuclear ex vivo magnetic resonance spectroscopy (MRS) of cancer cells, xenografts, human cancer tissue, and biofluids is a rapidly expanding field that is providing unique insights into cancer. Starting from the 1970s, the field has continued to ... ...

Abstract	Multinuclear ex vivo magnetic resonance spectroscopy (MRS) of cancer cells, xenografts, human cancer tissue, and biofluids is a rapidly expanding field that is providing unique insights into cancer. Starting from the 1970s, the field has continued to evolve as a stand-alone technology or as a complement to in vivo MRS to characterize the metabolome of cancer cells, cancer-associated stromal cells, immune cells, tumors, biofluids and, more recently, changes in the metabolome of organs induced by cancers. Here, we review some of the insights into cancer obtained with ex vivo MRS and provide a perspective of future directions. Ex vivo MRS of cells and tumors provides opportunities to understand the role of metabolism in cancer immune surveillance and immunotherapy. With advances in computational capabilities, the integration of artificial intelligence to identify differences in multinuclear spectral patterns, especially in easily accessible biofluids, is providing exciting advances in detection and monitoring response to treatment. Metabolotheranostics to target cancers and to normalize metabolic changes in organs induced by cancers to prevent cancer-induced morbidity are other areas of future development.
MeSH term(s)	Humans ; Artificial Intelligence ; Magnetic Resonance Spectroscopy/methods ; Neoplasms ; Metabolome
Language	English
Publishing date	2022-03-25
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.4724
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Zs.A 2869: 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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Article: The PD-L1 metabolic interactome intersects with choline metabolism and inflammation.

Pacheco-Torres, Jesus / Penet, Marie-France / Mironchik, Yelena / Krishnamachary, Balaji / Bhujwalla, Zaver M

Cancer & metabolism

2021 Volume 9, Issue 1, Page(s) 10

Abstract: Background: Harnessing the power of the immune system by using immune checkpoint inhibitors has resulted in some of the most exciting advances in cancer treatment. The full potential of this approach has, however, not been fully realized for treating ... ...

Abstract	Background: Harnessing the power of the immune system by using immune checkpoint inhibitors has resulted in some of the most exciting advances in cancer treatment. The full potential of this approach has, however, not been fully realized for treating many cancers such as pancreatic and breast cancer. Cancer metabolism influences many aspects of cancer progression including immune surveillance. An expanded understanding of how cancer metabolism can directly impact immune checkpoints may allow further optimization of immunotherapy. We therefore investigated, for the first time, the relationship between the overexpression of choline kinase-α (Chk-α), an enzyme observed in most cancers, and the expression of the immune checkpoint PD-L1. Methods: We used small interfering RNA to downregulate Chk-α, PD-L1, or both in two triple-negative human breast cancer cell lines (MDA-MB-231 and SUM-149) and two human pancreatic ductal adenocarcinoma cell lines (Pa09C and Pa20C). The effects of the downregulation were studied at the genomic, proteomic, and metabolomic levels. The findings were compared with the results obtained by the analysis of public data from The Cancer Genome Atlas Program. Results: We identified an inverse dependence between Chk-α and PD-L1 at the genomic, proteomic, and metabolomic levels. We also found that prostaglandin-endoperoxide synthase 2 (COX-2) and transforming growth factor beta (TGF-β) play an important role in this relationship. We independently confirmed this relationship in human cancers by analyzing data from The Cancer Genome Atlas Program. Conclusions: Our data identified previously unknown roles of PD-L1 in cancer cell metabolic reprogramming, and revealed the immunosuppressive increased PD-L1 effect of Chk-α downregulation. These data suggest that PD-L1 regulation of metabolism may be mediated through Chk-α, COX-2, and TGF-β. The observations provide new insights that can be applied to the rational design of combinatorial therapies targeting immune checkpoints and cancer metabolism.
Language	English
Publishing date	2021-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2700141-6
ISSN	2049-3002
ISSN	2049-3002
DOI	10.1186/s40170-021-00245-w
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Article: PD-L1 siRNA Theranostics With a Dextran Nanoparticle Highlights the Importance of Nanoparticle Delivery for Effective Tumor PD-L1 Downregulation.

Pacheco-Torres, Jesus / Penet, Marie-France / Krishnamachary, Balaji / Mironchik, Yelena / Chen, Zhihang / Bhujwalla, Zaver M

Frontiers in oncology

2021 Volume 10, Page(s) 614365

Abstract: Purpose: The inhibition of immune checkpoints such as programmed cell death ligand-1 (PD-L1/CD274) with antibodies is providing novel opportunities to expose cancer cells to the immune system. Antibody based checkpoint blockade can, however, result in ... ...

Abstract	Purpose: The inhibition of immune checkpoints such as programmed cell death ligand-1 (PD-L1/CD274) with antibodies is providing novel opportunities to expose cancer cells to the immune system. Antibody based checkpoint blockade can, however, result in serious autoimmune complications because normal tissues also express immune checkpoints. As sequence-specific gene-silencing agents, the availability of siRNA has significantly expanded the specificity and range of "druggable" targets making them promising agents for precision medicine in cancer. Here, we have demonstrated the ability of a novel biodegradable dextran based theranostic nanoparticle (NP) to deliver siRNA downregulating PD-L1 in tumors. Optical imaging highlighted the importance of NP delivery and accumulation in tumors to achieve effective downregulation with siRNA NPs, and demonstrated low delivery and accumulation in several PD-L1 expressing normal tissues. Methods: The dextran scaffold was functionalized with small molecules containing amine groups through acetal bonds. The NP was decorated with a Cy5.5 NIR probe allowing visualization of NP delivery, accumulation, and biodistribution. MDA-MB-231 triple negative human breast cancer cells were inoculated orthotopically or subcutaneously to achieve differences in vascular delivery in the tumors. Molecular characterization of PD-L1 mRNA and protein expression in cancer cells and tumors was performed with qRT-PCR and immunoblot analysis. Results: The PD-L1 siRNA dextran NPs effectively downregulated PD-L1 in MDA-MB-231 cells. We identified a significant correlation between NP delivery and accumulation, and the extent of PD-L1 downregulation, with Conclusions: Here we have demonstrated, for the first time, the feasibility of downregulating PD-L1 in tumors using siRNA delivered with a biodegradable dextran polymer that was decorated with an imaging reporter. Our data demonstrate the importance of tumor NP delivery and accumulation in achieving effective downregulation, highlighting the importance of imaging in siRNA NP delivery. Effective delivery of these siRNA carrying NPs in the tumor but not in normal tissues may mitigate some of the side-effects of immune checkpoint inhibitors by sparing PD-L1 inhibition in these tissues.
Language	English
Publishing date	2021-02-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.614365
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Article: VEGF Overexpression Significantly Increases Nanoparticle-Mediated siRNA Delivery and Target-Gene Downregulation.

Tan, Shanshan / Chen, Zhihang / Mironchik, Yelena / Mori, Noriko / Penet, Marie-France / Si, Ge / Krishnamachary, Balaji / Bhujwalla, Zaver M

Pharmaceutics

2022 Volume 14, Issue 6

Abstract: The availability of nanoparticles (NPs) to deliver small interfering RNA (siRNA) has significantly expanded the specificity and range of 'druggable' targets for precision medicine in cancer. This is especially important for cancers such as triple ... ...

Abstract	The availability of nanoparticles (NPs) to deliver small interfering RNA (siRNA) has significantly expanded the specificity and range of 'druggable' targets for precision medicine in cancer. This is especially important for cancers such as triple negative breast cancer (TNBC) for which there are no targeted treatments. Our purpose here was to understand the role of tumor vasculature and vascular endothelial growth factor (VEGF) overexpression in a TNBC xenograft in improving the delivery and function of siRNA NPs using in vivo as well as ex vivo imaging. We used triple negative MDA-MB-231 human breast cancer xenografts derived from cells engineered to overexpress VEGF to understand the role of VEGF and vascularization in NP delivery and function. We used polyethylene glycol (PEG) conjugated polyethylenimine (PEI) NPs to deliver siRNA that downregulates choline kinase alpha (Chkα), an enzyme that is associated with malignant transformation and tumor progression. Because Chkα converts choline to phosphocholine, effective delivery of Chkα siRNA NPs resulted in functional changes of a significant decrease in phosphocholine and total choline that was detected with
Language	English
Publishing date	2022-06-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14061260
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Article ; Online: Cancer cachexia, recent advances, and future directions.

Penet, Marie-France / Bhujwalla, Zaver M

Cancer journal (Sudbury, Mass.)

2015 Volume 21, Issue 2, Page(s) 117–122

Abstract: Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number ... ...

Abstract	Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number of studies related to cancer cachexia, the underlying mechanisms are still poorly defined, and therapeutic options are limited. This review focuses on recent studies investigating mechanisms and pathways in cancer cachexia. The role of molecular and functional imaging in identifying cachexia at an earlier stage, in identifying potential metabolic targets and pathways, and in assessing treatment efficacy is also reviewed.
MeSH term(s)	Animals ; Cachexia/diagnosis ; Cachexia/etiology ; Cachexia/metabolism ; Cachexia/therapy ; Diagnostic Imaging ; Energy Metabolism ; Humans ; Neoplasms/complications ; Neoplasms/diagnosis ; Neoplasms/metabolism ; Neoplasms/therapy
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2018400-1
ISSN	1540-336X ; 1528-9117 ; 1081-4442
ISSN (online)	1540-336X
ISSN	1528-9117 ; 1081-4442
DOI	10.1097/PPO.0000000000000100
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Zs.A 4470: 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)
Zs.MO 163: Show issues

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Article ; Online: PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity.

Parkins, Katie M / Krishnamachary, Balaji / Jacob, Desmond / Kakkad, Samata M / Solaiyappan, Meiyappan / Mishra, Akhilesh / Mironchik, Yelena / Penet, Marie-France / McMahon, Michael T / Knopf, Philipp / Pichler, Bernd J / Nimmagadda, Sridhar / Bhujwalla, Zaver M

Radiology. Imaging cancer

2023 Volume 5, Issue 4, Page(s) e220138

Abstract: Purpose To examine the association between hypoxia and programmed cell death ligand 1 (PD-L1) expression using bioluminescence imaging (BLI) and PET/MRI in a syngeneic mouse model of triple-negative breast cancer (TNBC). Materials and Methods PET/MRI and ...

Abstract	Purpose To examine the association between hypoxia and programmed cell death ligand 1 (PD-L1) expression using bioluminescence imaging (BLI) and PET/MRI in a syngeneic mouse model of triple-negative breast cancer (TNBC). Materials and Methods PET/MRI and optical imaging were used to determine the role of hypoxia in altering PD-L1 expression using a syngeneic TNBC model engineered to express luciferase under hypoxia. Results Imaging showed a close spatial association between areas of hypoxia and increased PD-L1 expression in the syngeneic murine (4T1) tumor model. Mouse and human TNBC cells exposed to hypoxia exhibited a significant increase in PD-L1 expression, consistent with the in vivo imaging data. The role of hypoxia in increasing PD-L1 expression was further confirmed by using The Cancer Genome Atlas analyses of different human TNBCs. Conclusion These results have identified the potential role of hypoxia in contributing to PD-L1 heterogeneity in tumors by increasing cancer cell PD-L1 expression.
MeSH term(s)	Humans ; Animals ; Mice ; Triple Negative Breast Neoplasms/diagnostic imaging ; Triple Negative Breast Neoplasms/genetics ; B7-H1 Antigen/genetics ; Ligands ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Hypoxia ; Apoptosis
Chemical Substances	B7-H1 Antigen ; Ligands
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article
ISSN	2638-616X
ISSN (online)	2638-616X
DOI	10.1148/rycan.220138
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