Lithium ions: A novel treatment for pheochromocytomas and paragangliomas

Kappes, Ashley; Vaccaro, Abram; Kunnimalaiyaan, Muthusamy; Chen, Herbert

doi:10.1016/j.surg.2006.12.005

Cited by 25 publications

(33 citation statements)

References 14 publications

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“…Radiofrequency ablation of hepatic and bony metastases has shown symptomatic relief in some patients [144]. Current studies focus on targeted pharmacologic interventions of specific pathways within pheochromocytoma cells, specifically Raf-1 [161], glycogen synthase kinase-3␤ [162], and Notch-1 [163]. These pathways are currently being targeted in clinical trials for carcinoids and medullary thyroid cancer, and future experiments will be directed toward clinical applications of these treatments.…”

Section: Future Directionsmentioning

confidence: 99%

Pheochromocytoma: Current Approaches and Future Directions

et al. 2008

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After completing this course, the reader should be able to:1. Use current practice methods in the diagnosis of pheochromocytomas.2. Employ current practice methods in the treatment of pheochromocytomas.3. Evaluate the current molecular research that contributes to the treatment of pheochromocytomas.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTPheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Because of the excess secretion of hormones, these tumors often cause debilitating symptoms and a poor quality of life. While medical management plays a significant role in the treatment of pheochromocytoma patients, surgical excision remains the only cure. Improved medical management and surgical techniques and an increased understanding of hereditary disease have improved the outcome of pheochromocytoma patients with benign disease; however, the outcome of patients with malignant disease remains poor. In this review, we discuss the presentation, diagnosis, management, and future directions in the management of this disease. The Oncologist

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Section: Future Directionsmentioning

confidence: 99%

Pheochromocytoma: Current Approaches and Future Directions

et al. 2008

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“…In fact, the risk of cancer development among psychiatric patients treated with lithium salts, long known as an inhibitor of GSK-3␤, 6 is significantly lower than that in the general population, suggesting that inhibition of GSK-3␤ may have a generally protective effect toward carcinogenesis. 7 Accordingly, recent studies show that GSK-3␤ inhibitors lead to significant reduction in cell growth and proliferation of prostate, 8 pancreatic, 9 colorectal, 10 ovarian, 11 medullary thyroid, 12 and pheochromocytoma 13 cancer cell lines and that GSK-3␤ activity is essential for maintenance of a subset of leukemias. 14 The first role identified for GSK-3␤ almost 30 years ago recognized it as a crucial factor in glucose metabolism, being the kinase that phosphorylates and inactivates glycogen synthase, the first enzyme in glycogen biosynthesis.…”

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confidence: 99%

Nutritional Limitation Sensitizes Mammalian Cells to GSK-3β Inhibitors and Leads to Growth Impairment

Candia

Minopoli

Verga

et al. 2011

The American Journal of Pathology

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The serine/threonine kinase GSK-3␤ was initially described as a key enzyme involved in glucose metabolism, but it is now known to regulate a wide range of biological processes, including proliferation and apoptosis. We previously reported a transformation-dependent cell death induced by glucose limitation in K-ras-transformed NIH3T3. To address the mechanism of this phenomenon, we analyzed GSK-3␤ regulation in these cells in conditions of high versus low glucose availability. We found that glucose depletion caused a marked inhibition of GSK-3␤ through posttranslational mechanisms and that this inhibition was much less pronounced in normal cells. Further inhibition of GSK-3␤ with lithium chloride, combined with glucose shortage, caused specific activation of AMPactivated protein kinase and significant suppression of proliferation in transformed but not normal cells. The cooperative effect of lithium and low glucose availability on cell growth did not seem to depend exclusively on ras pathway activation because two human cell lines, A549 and MDA-MB-231, both harboring an activated ras gene, showed very different sensitivity to lithium. These findings thus provide a rationale to further analyze the biochemical bases for combined glucose deprivation and GSK-3␤ inhibition as a new approach to control transformed cell growth.

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“…This finding suggests that the targeted inhibition of autophagy may be a therapeutic option for increasing the effectiveness of and surmounting resistance to sunitinib in the treatment of pheochromocytomas (Ikeda et al 2013). Although lithium was also proposed as a treatment option for pheochromocytomas due to its ability to inhibit PC12 cell growth in culture (Kappes et al 2007), the doses used in that paper were well outside the established therapeutic window for lithium use. When given in dosages within its therapeutic window, lithium promoted the proliferation of PC12 cells in culture and protected them from toxin-induced cell death (Fabrizi et al 2014).…”

Section: Autophagy In Adrenal Cancermentioning

confidence: 97%

“…Moreover, the protective effect of lithium seemed to be mediated through its induction of autophagy as a mechanism to cope with cell stress in response to a lack of nutrients due to overgrowth, as well as toxic compounds (Fabrizi et al 2014). This discrepancy between the findings of Kappes et al (2007) and Fabrizi et al (2014) may be indicative of the fine line between autophagy as a protective mechanism and overstimulation of autophagy leading to programmed cell death. Due to its propensity for activating autophagy as a defense mechanism at therapeutically viable doses, contrary to the suggestion of Kappes et al (2007), the use of lithium as a treatment for pheochromocytomas is unlikely to be effective.…”

Section: Autophagy In Adrenal Cancermentioning

confidence: 99%

Autophagy in endocrine tumors

Weckman¹,

Rotondo²,

Ieva³

et al. 2015

Endocrine-Related Cancer

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Autophagy is an important intracellular process involving the degradation of cytoplasmic components. It is involved in both physiological and pathological conditions, including cancer. The role of autophagy in cancer is described as a 'double-edged sword,' a term that reflects its known participation in tumor suppression, tumor survival and tumor cell proliferation. Available research regarding autophagy in endocrine cancer supports this concept. Autophagy shows promise as a novel therapeutic target in different types of endocrine cancer, inhibiting or increasing treatment efficacy in a context-and cell-typedependent manner. At present, however, there is very little research concerning autophagy in endocrine tumors. No research was reported connecting autophagy to some of the tumors of the endocrine glands such as the pancreas and ovary. This review aims to elucidate the roles of autophagy in different types of endocrine cancer and highlight the need for increased research in the field.

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Lithium ions: A novel treatment for pheochromocytomas and paragangliomas

Cited by 25 publications

References 14 publications

Pheochromocytoma: Current Approaches and Future Directions

Pheochromocytoma: Current Approaches and Future Directions

Nutritional Limitation Sensitizes Mammalian Cells to GSK-3β Inhibitors and Leads to Growth Impairment

Autophagy in endocrine tumors

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