Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

Zhou, Guan-Qun; Tang, Ling‐Long; Mao, Yan‐Ping; Chen, Lei; Li, Wen‐Fei; Sun, Ying; Liu, Lizhi; Li, Li; Lin, Aihua; Ma, Jun

doi:10.1016/j.ijrobp.2011.06.1967

Cited by 102 publications

(114 citation statements)

References 18 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: Discussionsupporting

confidence: 53%

“…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: Discussionsupporting

confidence: 53%

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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“…Therefore, it is important to identify other prognostic factors to improve the ability of the TNM staging system to predict prognosis. In recent years, there have been several published reports focusing on the correlation between the prognosis of NPC patients treated with IMRT and tumour-or host-related factors, such as the primary tumour volume (GTV-P) (Guo et al 2012;Chen et al 2011), the maximum standardized uptake value of the primary tumour (SUVmax-P), which is tested by 18 F-FDG PET/CT , weight loss during treatment (Qiu et al 2011), baseline serum LDH levels Zhou et al 2012), and the albumin-globulin ratio before treatment (pretreatment AGR) . The results of those studies indicated that advanced large GTV-P (Guo et al 2012;Chen et al 2011), high SUVmax-P , high weight loss during treatment (Qiu et al 2011), high baseline serum LDH levels Zhou et al 2012) and lower pretreatment AGR all are predictors of a poor prognosis and could be used to facilitate treatment options when combined with the TNM staging system.…”

Section: Discussionmentioning

confidence: 99%

The value of the Prognostic Nutritional Index (PNI) in predicting outcomes and guiding the treatment strategy of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy

Miao

Xiao

Wang

et al. 2017

J Cancer Res Clin Oncol

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“…enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A Studies have shown that the LDHA expression in cancer cells is associated with radiotherapy sensitivity (15). In addition, it has been reported LDHA contributed to paclitaxel resistance in breast cancer, inhibition of LDHA by oxamate overrides the chemoresistance (16).…”

Section: Targeting Glucose Metabolism In Chondrosarcoma Cellsmentioning

confidence: 99%

Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A

Hua¹,

Liu²,

Li³

et al. 2014

Oncology Reports

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Abstract. Chondrosarcoma is a malignant cartilage-forming cancer composed of cells derived from transformed cells that produce cartilage. Conventional chemotherapy and radiotherapy have very limited efficacy in patients with advanced chondrosarcoma. In the present study, we reported a novel therapeutic approach in the treatment of chondrosarcoma cells. We detected that lactate dehydrogenase-A (LDHA) is highly active in chondrosarcoma cells and chondrosarcoma patient samples compared with normal chondrocyte cell lines and primary human chondrocyte. Moreover, chondrosarcoma cells exhibited elevated levels of LDHA expression under doxorubicin treatment. To further explore the mechanisms, we generated doxorubicin-resistant cells from SW1353 chondrosarcoma cell line. Notably, the activity and expression of LDHA are upregulated in doxorubicin-resistant cells. Moreover, our data showed a strong correlation between glucose metabolism and doxorubicin resistance in chondrosarcoma cells; doxorubicinresistant cells displayed highly activated glucose metabolism and depended more on glucose supply. Finally, we reported a synergistic effect produced by incorporating doxorubicin with glycolysis inhibitors-oxamate in the combined treatment of chondrosarcoma cells in vitro and in vivo. In summary, the present study may aid in the development of new approaches using the combination of chemotherapeutic agents for the treatment of chondrosarcoma patients.

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Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

Cited by 102 publications

References 18 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

The value of the Prognostic Nutritional Index (PNI) in predicting outcomes and guiding the treatment strategy of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy

Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A

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