Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma

Zhuo, Yi; Lin, Lanying; Wei, Shushan; Zhang, Mingwei

doi:10.1097/md.0000000000005706

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…A recent meta-analysis showed that elevated serum LDH-A levels prior to chemotherapeutic treatment, are a significant prognostic factor in malignant mesothelioma. 57 However, to the best of our knowledge, the current research is the first study to demonstrate the prognostic role of LDH-A protein expression in tumour tissues from both MPM and DMPM patients.…”

Section: Discussionmentioning

confidence: 78%

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

et al. 2020

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Background Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. Results Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. Conclusions This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors.

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Section: Discussionmentioning

confidence: 78%

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

et al. 2020

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“…[3] For treatment biomarker of NSCLC, many studies have identified the driving genes of lung cancer, including epidermal growth factor receptor (EGFR) gene mutation, anaplastic lymphoma kinase ( ALK) gene rearrangement. [4,5] At the same time, other studies have confirmed the potential markers such as phosphatase and tensin homolog on chromosometen (PTEN), ribonucleotide reductase M1 (RRM1) and excision repair cross-complementing 1 (ERCC1) as prognostic markers in patients with lung cancer,especially for those who received chemotherapy [6,7,8,9] However, these indicators are not widely used clinically. Therefore, it is very important to find a simple and easy marker which is not only easy to be measured, but also can be used to identify specific types of patients.…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein is a significant predictor of improved survival in patients with advanced non-small cell lung cancer.

2019

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This study tries to evaluate the associations between circulating C-reactive protein (CRP) and the overall survival of patients with non-small cell lung cancer (NSCLC). One hundred ninety-two patients with advanced NSCLC who treated with chemotherapy were enrolled in this study. The cut-off value of CRP concentration was 5.0 mg/L. The patients were divided into low, intermediate and high 3 groups respectively according to the baseline level of CRP before the treatment. Kaplan–Meier analysis and Cox proportional-hazard models were used to evaluate the relationship between the CRP and overall survival time of patients. After adjusting for age, gender, smoking history, pathologic type, CRP was a significant independent impact which predicts the survival prognosis of patients with NSCLC. For all patients, the hazard ratio with high CRP levels for NSCLC-specific survival was 1.83 [95%confidenceinterval (CI) = 0.96, 3.48] compared with low CRP levels. The level of CRP was significantly correlated with survival time (hazard ratio = 1.77; 95% CI = 0.73, 4.26) for the patient with first-line chemotherapy. Patients with high level of circulating CRP also responded poorly to chemotherapy. A high level of circulating CRP was associated with a poor response and worse survival in patients with NSCLC.

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“…A meta-analysis conducted by Yi et al demonstrated a negative relationship between LDH level before initiating treatment and poor survival. They suggested that pretreatment LDH level can be valuable as a predictor of prognosis in such patients [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Malignant primary pericardial mesothelioma presenting as effusive constrictive pericarditis: a case report study

Savarrakhsh

Vakilpour

Davani

et al. 2021

J Cardiothorac Surg

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Background Primary pericardial mesothelioma (PPM) is a rare malignancy with a high prevalence of mortality. The diagnosis is usually challenging using a variety of imaging modalities and invasive procedures and is generally performed at the later stages of the disease or in autopsy. This case study points to an unconventional presentation of PPM and the challenges in diagnosing this rare mortal malignancy. Case presentation This study presents a 44-year-old woman with no remarkable medical history with an initial diagnosis of effusive constrictive pericarditis at first hospitalization. Imaging evaluations, including transthoracic echocardiography and chest computed tomography scan, demonstrated visible thickened pericardium, pericardial effusion, and mass-like lesions in pericardium and mediastinum. The definite diagnosis of primary pericardial mesothelioma was established after pericardiectomy and histopathology examinations. Chemotherapy with pemetrexed and carboplatin was administrated to the patient, and she has been through four cycles of chemotherapy with no complications to date. Conclusion Constrictive pericarditis is an uncommon presentation of PPM. Due to the high mortality rate and late presentation, difficulties and uncertainties in diagnosis, being aware of this rare malignant entity in different cardiac manifestations, particularly when there is no clear explanation or response to treatment in such conditions, is highly important.

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Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma

Cited by 11 publications

References 35 publications

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

C-reactive protein is a significant predictor of improved survival in patients with advanced non-small cell lung cancer.

Malignant primary pericardial mesothelioma presenting as effusive constrictive pericarditis: a case report study

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