Serum Lactate Dehydrogenase Level is a Prognostic Factor in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

Turen, Selahattin; Özyar, Enis; Altundağ, Kadri̇; Güllü, İbrahi̇m; Atahan, I. Lale

doi:10.1080/07357900701209103

Cited by 39 publications

(31 citation statements)

References 29 publications

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“…Several studies have shown that serum LDH may be an ominous prognostic marker in malignant tumors [24], i.e. serum LDH is a prediction factor for the response of chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma [25] and advanced oesophageal cancer [26]. Elevated serum LDH also showed correlation with survival time of terminally ill cancer patients [27] and with the clinical stage of lung cancer [28].…”

Section: Discussionmentioning

confidence: 98%

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

et al. 2009

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5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, resistance to this drug is a major obstacle in CRC chemotherapy. Accurate prediction of response to 5-FU would avoid unnecessary chemotherapy and allow the selection of other effective drugs. To identify a candidate predictor of 5-FU resistance, we isolated secreted proteins that were up- or downregulated in a 5-FU-resistant cancer cell line, compared with the parent cell line (SNU-C4), using a stable isotope-coded labeling protocol. For validating the clinical applicability of this method, levels of the identified proteins were determined in the sera of 46 patients treated with 5-FU. In total, 238 proteins with molecular weights ranging from 50 to 75 kDa were identified. Among these, 45 and 35 secreted proteins were up- and downregulated in the 5-FU-resistant cell line, respectively. We observed significant upregulation of glycolytic enzymes, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase M2 (PK-M2), transketolase, and NADP(+)-dependent malic enzyme 1. In particular, the level of PK-M2, a key enzyme in the glycolytic pathway, showed an increasing tendency in both sera and tissues from CRC patients displaying no response to 5-FU-based chemotherapy (progressive and stable disease cases), compared with that in complete or partial responders to 5-FU-based chemotherapy; however, it did not reach the statistical significance. In conclusion, increasing pattern of PK-M2 observed with 5-FU resistance induced in vitro and in sera and tissues from CRC patients displaying poor response to 5-FU-based chemotherapy suggest the relevance of dysregulated glycolysis and 5-FU-resistant CRC.

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Section: Discussionmentioning

confidence: 98%

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

et al. 2009

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“…LDH5 is upregulated in cancers (Koukourakis et al 2005a) which ensures continued glycolysis irrespective of the oxygen concentration (Dang and Semenza 1999;Robey et al 2005;Schulz et al 2006). Elevated serum LDH levels have been shown to correlate with poor prognosis in patients with pancreatic, renal, nasopharyngeal, and lung carcinoma amongst others (Tas et al 2001a, b;Turen et al 2007;Motzer et al 1999).…”

Section: Pfk-1mentioning

confidence: 97%

Cancer’s craving for sugar: an opportunity for clinical exploitation

Yeluri

Madhok

Prasad

et al. 2009

J Cancer Res Clin Oncol

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More than 80 years ago, Otto Warburg described the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions, a process subsequently referred to as the Warburg effect or aerobic glycolysis. The exact molecular mechanisms underlying cancers reliance on glycolysis remains unclear, but is likely a combination of an epigenetic response to the hypoxic tumour environment in combination with direct oncogenic stimulation. The aim of the current manuscript is to review the normal process of glycolysis and highlight the alterations that occur with malignant transformation, to consider the potential advantages of glycolytic respiration for cancer cell survival, and finally to explore areas where altered glucose metabolism can be exploited for clinical benefit.

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“…All these uncertainties highlighted the necessity of additional investigation in prospective setting. With further research into other predicting factors of NPC, such as tumour volume (21), serum lactate dehydrogenase (22), comorbidity (23) and Epstein-Barr virus Deoxyribonucleic acid (EBV-DNA) (24)(25)(26) and other molecular prognostic markers, it is likely that these will be taken in conjunction with stage classification in grouping patients into different prognostic groups, each with different recommended treatment. This kind of approach has been adopted for patients with human papillomavirus-related oropharyngeal carcinoma, as have been reported by Huang et al (27) from Canada.…”

Section: Discussionmentioning

confidence: 99%

Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era

Guo¹,

Lu²,

Shen³

et al. 2016

Jpn. J. Clin. Oncol.

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Objectives: To evaluate the long-term survival and the role of chemotherapy in nasopharyngeal carcinoma (NPC) patients in Stage II treated by intensity-modulated radiation therapy (IMRT). Methods: Three hundred and eleven NPC patients in Stage II were reviewed. All were treated with IMRT with or without chemotherapy, with 191, 20 and 100 patients being defined as T1N1M0, T2N0M0 and T2N1M0 stage, respectively. Results: At a median follow-up of 57 months, the 5-year overall survival, disease-specific survival, distant metastasis-free survival, loco-regional relapse-free survival (LRRFS) and progression-free survival were 91.1, 93.5, 90.6, 95.9 and 87.6%, respectively. T2N1 patients had significant poorer survival outcomes than T1N1 patients, with T2N0 patients in between. Further analysis showed that the addition of chemotherapy could only improve LRRFS [hazard ratio (HR) 0.263, 95% confidence interval (CI) 0.083-0.839, P = 0.024], especially for T1N1 patients (HR 0.209, 95% CI 0.046-0.954, P = 0.043). For those in the T2N1M0 group, chemotherapy, as used in our series, added no benefit to any endpoint. Conclusions: IMRT in NPC patients in Stage II was quite therapeutic; however, different subgroups have distinct survival outcomes. Distant metastasis was the main failure pattern, especially for those with T2N1 disease, and the chemotherapy currently in use failed to treat subclinical metastatic foci effectively. Further prospective study is warranted to find out the role and the optimal schedule of chemotherapy in this subgroup of patients.

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Serum Lactate Dehydrogenase Level is a Prognostic Factor in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

Cited by 39 publications

References 29 publications

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

Cancer’s craving for sugar: an opportunity for clinical exploitation

Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era

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