A5050077770- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Bone health and treatments
- Prostate Cancer Treatment and Research
- Fibroblast Growth Factor Research
- Radiopharmaceutical Chemistry and Applications
- Epigenetics and DNA Methylation
- Bone Metabolism and Diseases
- Lung Cancer Research Studies
- Protease and Inhibitor Mechanisms
- Nanoplatforms for cancer theranostics
- Bone and Dental Protein Studies
- Bone and Joint Diseases
- Click Chemistry and Applications
- Photochromic and Fluorescence Chemistry
- Eicosanoids and Hypertension Pharmacology
- Cancer Cells and Metastasis
- Lipid metabolism and biosynthesis
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- Hematological disorders and diagnostics
- Adipose Tissue and Metabolism
- Crystallization and Solubility Studies
- Peroxisome Proliferator-Activated Receptors
The Barbara Ann Karmanos Cancer Institute
2015-2025
Wayne State University
2015-2025
Indiana University School of Medicine
2016-2017
Oakland University
2001
University of Rochester
1999-2001
Incidence of skeletal metastases and death from prostate cancer greatly increases with age obesity, conditions which increase marrow adiposity. Bone adipocytes are metabolically active components bone metastatic niche that modulate the function neighboring cells; yet mechanisms their involvement in tumor behavior have not been explored. In this study, using experimental models intraosseous growth diet-induced we demonstrate promoting effects fat on progression tumors. We reveal exposure to...
A novel method for caging protease inhibitors is described. The complex [Ru(II)(bpy)(2)(1)(2)](PF(6))(2) (2) was prepared from the nitrile-based peptidomimetic inhibitor Ac-Phe-NHCH(2)CN (1). (1)H NMR, UV-vis, and IR spectroscopic mass spectrometric data confirmed that 2 equiv of 1 bind to Ru(II) through nitrile functional group. Complex shows excellent stability in aqueous solution dark fast release upon irradiation with visible light. As a result binding center, nitriles are caged, does...
Dual action agents containing a cysteine protease inhibitor and Ru-based photosensitizer for photodynamic therapy (PDT) were designed, synthesized, validated in 2D culture 3D functional imaging assays of triple-negative human breast cancer (TNBC). These combination deliver release PDT to tumor cells cause cell death upon irradiation with visible light, while at the same time inactivating cathespin B (CTSB), strongly associated invasive metastatic behavior. In total five complexes synthesized...
// Jonathan D. Diedrich 1,3 , Erandi Rajagurubandara 1 Mackenzie K. Herroon Gargi Mahapatra 2 Maik Hüttemann 1,2 and Izabela Podgorski Department of Pharmacology, Wayne State University School Medicine, Detroit, MI, USA Center for Molecular Medicine Genetics, 3 Karmanos Cancer Institute, Correspondence to: Podgorski, email: Keywords : bone marrow adipocytes, metastasis, prostate cancer, glycolysis, Warburg effect Received August 15, 2016 Accepted 21, Published 30, Abstract Metabolic...
Abstract Stromal-derived hepatocyte growth factor (HGF) acting through its specific proto-oncogene receptor c-Met has been suggested to play a paracrine role in the regulation of tumor cell migration and invasion. The transition from preinvasive ductal carcinoma situ (DCIS) invasive breast is marked by infiltration stromal fibroblasts loss basement membrane. We hypothesized that HGF produced infiltrating may alter proteolytic pathways DCIS cells, and, study this hypothesis, established...
New Ru(ii)-caged abiraterone complexes were synthesized that exhibit strong absorption in the visible region and release steroidal CYP17A1 inhibitor upon exposure to low energy light buffer prostate cancer cells. Photoinduced results binding its target an inhibitory mode.
A chiral porphyrazine (pz), H 2 [pz( trans - B )] (247), has been prepared that exhibits preferential in vivo accumulation the cells of tumors. Pz 247 near-infrared (NIR) emission with λ > 700 nm required wavelength range for maximum tissue penetration. When MDA-MB-231 breast tumor are treated 247, agent shows strong intracellular fluorescence an maximum, 704 nm, which indicates it localizes within a hydrophobic microenvironment. is shown to associate lipophilic core LDL and undergo...
Ruthenium(II) tris(2-pyridylmethyl)amine (TPA) is an effective caging group for nitriles that provides high levels of control over the enzyme activity with light. Two caged were prepared, [Ru(TPA)(MeCN)2](PF6)2 (1) and [Ru(TPA)(3)2](PF6)2 (2), where 3 cathepsin K inhibitor Cbz-Leu-NHCH2CN, characterized by various spectroscopic techniques mass spectrometry. Both 1 2 show release a single nitrile within 20 min irradiation 365 nm Complex acts as potent, photoactivated human K. IC50 values...
Abstract Light‐activated inhibition of cathepsin activity was demonstrated in a cell‐based assay. Inhibitors K, Cbz‐Leu‐NHCH 2 CN ( ) and Cbz‐Leu‐Ser(OBn)‐CN 3 ), were caged within the complexes cis ‐[Ru(bpy) ]Cl 4 ](BF 5 (bpy=2,2′‐bipyridine) as 1:1 mixtures Δ Λ stereoisomers. Complexes characterized by 1 H NMR, IR, UV/Vis spectroscopies electrospray mass spectrometry. Photochemical experiments confirm that releases two molecules upon exposure to visible light for 15 min, whereas release...
Prostate cancers metastasize to bone leading osteolysis. Here we assessed proteolysis of DOcollagen I (a matrix protein) and, for comparison, DO-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, this degradation was reduced inhibitors metallo, serine, cysteine proteases. Because secretion the protease cathepsin B is increased breast fibroblasts grown on collagen gels, analyzed levels and gels. Levels only DU145 cells-cells that expressed highest...
Light provides control over irreversible inhibition with Ru(<sc>ii</sc>)-caged epoxysuccinyl compounds and release of a Ru(<sc>ii</sc>) complex from protein–inhibitor conjugate.
Adipocyte-tumor cell cross-talk is one of the critical mediators tumor progression and an emerging facilitator therapy evasion. Tumor cells that metastasize to adipocyte-rich bone marrow take advantage interplay between metabolic inflammatory pathways activate prosurvival mechanisms allow them thrive escape therapy. Using in vitro vivo models adiposity, we demonstrate metastatic prostate carcinoma engage adipocytes a functional promotes IL1β expression cells. Tumor-supplied contributes...
Acquired resistance to apoptotic agents is a long-standing challenge in cancer treatment. Cathepsin B (CTSB) an enzyme which, among many essential functions, promotes apoptosis during cellular stress through regulation of intracellular proteolytic networks on the minute time scale. Recent data indicate that CTSB inhibition may be promising method steer cells away from death toward necrosis, mechanism cell can overcome agents, stimulate immune response and promote antitumor immunity....
Tumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium rhodium complexes on TAMs have not been well characterized. To address this gap in field, panel 22 dirhodium were screened against three subtypes macrophages, triple-negative breast normal tissue cells. Experiments carried out 2D biomimetic 3D co-culture experiments with without irradiation blue light. Leads identified cell-type-specific toxicity toward...