High pretreatment serum lactate dehydrogenase level correlates with disease relapse and predicts an inferior outcome in locally advanced nasopharyngeal carcinoma

Wan, Xiang; Li, Wei; Li, Hao; Dong, Min; Q, Lin; Xiao, Kun; Huang, Pei Yu; Wen, Jing; Li, Xing; Chen, Jie; Ruan, Dan; Lin, Ze; Chen, Zhan Hong; Liu, Quentin; Wu, Xiang; Hong, Ming

doi:10.1016/j.ejca.2013.03.008

Cited by 90 publications

(101 citation statements)

References 28 publications

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“…Previous studies revealed that LDH-A expression is elevated both in squamous cell head and neck cancer cells and the blood serum of NPC patients and is associated with poor prognosis (4,15,16). As anticipated, LDH inhibition by oxamate was found to impair cell growth and increase ROS production in NPC cells.…”

Section: Discussionmentioning

confidence: 71%

“…Regarding NPC, LDH-A was reported to be highly expressed in head and neck cancer cells and was found to be associated with local relapse, worse survival and distant metastasis (14). In addition, several studies have also demonstrated that an increased LDH serum level is a poor prognostic factor in NPC patients (15,16). However, to date, there is no research on whether inhibition of LDH-A impairs the growth of NPC cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells

et al. 2013

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Abstract. An elevated rate of glucose consumption and the dependency on aerobic glycolysis for ATP generation have long been observed in cancer cells, a phenomenon known as the Warburg effect. The altered energy metabolism in cancer cells provides an attractive opportunity for developing novel cancer therapeutic strategies. Lactate dehydrogenase (LDH), which catalyzes the transformation of pyruvate to lactate, plays a vital role in the process of glycolysis. It has been reported that the level of LDH-A expression is increased both in head and neck cancer cells and in the blood serum of nasopharyngeal carcinoma (NPC) patients, and is associated with poor prognosis. However, the effect of LDH-A inhibition on NPC cells remains unknown. Here, in the present study, we found that oxamate, a classical inhibitor of LDH-A, suppressed cell proliferation in a dose-and time-dependent manner both in CNE-1 and CNE-2 cells, two NPC cancer cell lines. LDH inhibition by oxamate induced G 2 /M cell cycle arrest via downregulation of the CDK1/cyclin B1 pathway and promoted apoptosis through enhancement of mitochondrial ROS generation. N-acetylcysteine, a specific scavenger of ROS, significantly blocked the growth inhibition effect induced by oxamate. We also identified that oxamate increased sensitivity to ionizing radiation in the two NPC cancer cell lines. Furthermore, we verified similar results in tumor xenograft models. Collectively, these results suggest that LDH-A may serve as a promising therapeutic target for NPC treatment.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells

et al. 2013

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“…In addition, a significant relationship between high levels of LDH and a higher incidence of liver and bone metastases was found in the case of advanced SCLCs [39]. Similarly, in patients with locally advanced nasopharyngeal carcinoma or metastatic colon cancer where treated with neoadjuvant chemotherapy combined with radiotherapy, high-serum LDH activity levels were an independent unfavorable risk factor for overall survival (OS) [40][41][42][43]. In the studies on the prognostic significance of pretreatment serum LDH levels in advanced colorectal cancer patients receiving chemotherapy combined with bevacizumab, the higher progression-free survival (PFS) rates in high-LDH patients were found to be correlated with the effect of bevacizumab, suggesting that antiangiogenic treatment was able to improve prognosis in this group of patients [41,44].…”

Section: Clinical Significance Of Total Ldh Activitymentioning

confidence: 95%

Lactate dehydrogenase 5: An old friend and a new hope in the war on cancer

2015

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“…In many malignant tumors, serum markers have been shown to be useful prognostic factors (Saif et al,1 (Li et al, 2012;Wan et al, 2013). Elevated levels of serum alkaline phosphatase (S-ALP) have been reported to predict poor outcomes in various malignant cancers, including prostate carcinoma, colorectal carcinoma, and malignant tumors in soft tissues of the extremities (Bacci et al, 2002;Saif et al, 2005;Sonpavde et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Pretreatment Serum Alkaline Phosphatase in Nasopharyngeal Carcinoma

Xie¹,

Wei²,

Xu-wei³

2014

Asian Pacific Journal of Cancer Prevention

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High pretreatment serum lactate dehydrogenase level correlates with disease relapse and predicts an inferior outcome in locally advanced nasopharyngeal carcinoma

Cited by 90 publications

References 28 publications

Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells

Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells

Lactate dehydrogenase 5: An old friend and a new hope in the war on cancer

Prognostic Value of Pretreatment Serum Alkaline Phosphatase in Nasopharyngeal Carcinoma

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