Selective acidification and de-energization of cancers by inhibition of monocarboxylate transporters (MCTs), mitochondrial pyruvate carrier (MPC)and Complex II of Electron Transport Chain (ETC). Development of a safe and reproducible method to selectively acidify the human melanoma xenografts and other cancers. Specifically, we seek to employ the natural tendency of melanomas and other tumors to convert glucose to lactate as a method for selective intracellular acidification of the tumor, which is known to potentiate tumor response to radiation therapy, hyperthermia as well as to chemotherapy with platinum, N-mustard and anthracyclines alkylating agents such as cisplatin, cyclophosphamide, melphalan and doxorubicin. In vivo 31Phosphorus Magnetic Resonance Spectroscopy demonstrated that human melanoma xenografts and other cancers such as breast, prostate and ovarian in immunosuppressed mice treated with the MCT and MPC inhibitor lonidamine (100 mg/kg, intraperitoneal) exhibit a sustained and tumor-selective decrease in pH, bioenergetics and subsequent sensitization with melphalan and doxorubicin in combination with lonidamine.
Xenografts development (melanoma, breast, prostate, ovarian, lymphoma etc.), cell culture, drug delivery, and tumor microinvironment.
Surface coil development compatible to animal scanner.
Proton, Phosphorus, Carbon Spectroscopy, Dynamic Contrast Enhanced (DCE) MRI, T-1, T-2 and Diffusion weighted MRI, in mice with subcutaneous tumor.
Diffusion tensor imaging and proton magnetic resonance spectroscopy in patients with brain abscess, brain tumor, meningitis, neurocysticercosis and liver failure on clinical scanner.
Measurement of test-retest reproducibility of SUV (Subsidized Uptake Value) on PET under clinical practice conditions in cancer patients.
Nath K, Nelson DS, Putt ME, Leeper DB, Garman B, Nathanson KL, Glickson JD: Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice. PLoS One 11(6), 2016.
Nancolas B, Guo L, Zhou R, Nath K, Nelson DS, Leeper DB, Blair IA, Glickson JD, Halestrap AP.: The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 473(7): 929-36, 2016.
De Brosse K, Nanga R, Bagga P, Nath K, Haris M, Marincola F, Schnall M, Hariharan H, Reddy R: Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo: A Biomarker for LDH Activity. Sci Rep. 6: 19517, 2016.
Guo L, Shestov AA, Worth AJ, Nath K, Nelson DS, Leeper DB, Glickson JD, Blair IA. : Inhibition of mitochondrial complex II by the anti-cancer agent lonidamine. J Biol Chem. 291(1): 42-57, 2016.
Alexander A Shestov, Seung-Cheol Lee, Kavindra Nath, Lili Guo, David Samuel Nelson, Jeffrey C Roman, Dennis B Leeper, Mariusz A Wasik, Ian A Blair, Jerry David Glickson: 13C MRS and LC-MS Flux Analysis of Tumor Intermediary Metabolism. Front. Oncol. 6(135), 2016.
Nath Kavindra, Nelson David S, Heitjan Daniel F, Leeper Dennis B, Zhou Rong, Glickson Jerry D: Lonidamine induces intracellular tumor acidification and ATP depletion in breast, prostate and ovarian cancer xenografts and potentiates response to doxorubicin. NMR in Biomedicine 28(3): 281-290, 2015.
Nath Kavindra, Nelson David S, Heitjan Daniel F, Zhou Rong, Leeper Dennis B, Glickson Jerry D. : Effects of hyperglycemia on lonidamine-induced acidification and de-energization of human melanoma xenografts and sensitization to melphalan. NMR in Biomedicine 28(3): 395-403, 2015.
Ting Liu, Kavindra Nath, Weixia Liu, Rong Zhou, I-Wei Chen: A study of the relationship of metabolic MR parameters to estrogen dependence in breast cancer xenografts. NMR in Biomedicine 28(9): 1087-96, 2015.
Haris Mohammad, Singh Anup, Mohammed Imran, Ittyerah Ranjit, Nath Kavindra, Nanga Ravi Prakash Reddy, Debrosse Catherine, Kogan Feliks, Cai Kejia, Poptani Harish, Reddy Damodar, Hariharan Hari, Reddy Ravinder: In vivo magnetic resonance imaging of tumor protease activity. Scientific Reports 4: 6081, 2014.
Haris Mohammad, Singh Anup, Cai Kejia, Nath Kavindra, Verma Gaurav, Nanga Ravi Prakash Reddy, Hariharan Hari, Detre John A, Epperson Neill, Reddy Ravinder: High resolution mapping of modafinil induced changes in glutamate level in rat brain. PloS One 9(7): e103154, 2014.
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Last updated: 08/09/2016
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