Relation between LDH and Mg as Factors of Interest in the Monitoring and Prognoses of Cancer

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Relation between LDH and Mg as Factors of Interest in the Monitoring and Prognoses of Cancer Aurelian Udristioiu, Emergency County Hospital Targu Jiu Romania, Clinical Laboratory Medical Analyses, E-mail: aurelianu2007@yahoo.com Sorina Comisel, UMF Craiova, Medicine Faculty, Endocrinology, Craiova, Romania, E-mail: sorinacomisel@hotmail.com Cristina Popescu, Medistar S.R.L Targu-Jiu, Biochemist Departement , Romania, kristinapopescu@yahoo.com Manole Cojocaru, Titu Maiorescu University, Medicine Faculty, Physiology, Bucharest, E-mail: manole.cojocaru@yahoo.com ABSTRACT Aim of this study was to evaluate the correlation between the serum levels of lactate dehydrogenase (LDH) and magnesium (Mg) in patients with diagnosed malignant diseases. Method: We analyzed these parameters on a cohort of patients (n = 75) comprising males (n= 36) and females (n=39) with a mean age of 57 years (SD= 12.5). Results In this study, 55 patients (73%) who received cancer therapy exhibited normal serum levels of Mg (normal value = 1.60-2.3 mg/dL; mean value = 2.2 mg/dL; SD = 0.2; p = 0.02). In contrast, 12 patients (16%), recently diagnosed with a malignant disease, who had not been treated, displayed high levels of serum Mg(mean value = 2.89 mg/dL). High serum LDH levels were observed in patients with recently diagnosed malignant diseases or unfavorable responses to cancer therapy (range = 240-1330 U/L; mean value = 787 U/L; SD =1.33; p = 0.002; normal values = 135-225 UL). Conclusion The total serum LDH and Mg levels can be used as markers for the onset of malignant diseases and for monitoring the response to cancer therapy. Keywords: Lactate dehydrogenase, Isocitrate dehydrogenase, CLL-Chronic lymphocytic leukemia, Acute promyelocytic leukemia, Transient receptor potential melastatin cation channel 6, Nicotinamide dehydrogenase,

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Methods We analyzed a cohort of patients (n = 75) comprising males (n = 36) and females (n =39) with a mean age of 57 years (SD = 12.5) who had cancer and were admitted to the oncology department. These patients were closely monitored twice weekly during treatment with specific cytostatic drugs of induction (using fluorouracil, leucovorin, oxaliplatin or rituximab) and once weekly during consolidation therapy, using specific analyses for different cancers. In addition, with the cooperation of the doctors and the patients, we performed beside hematological and biochemical tests, the CBC with differential counts, the levels of creatinine, uric acid, ions and electrolytes (potassium, chloride, calcium) and serum LDH and Mg, which may serve as markers for monitoring the progression of malignant diseases. The hematological parameters were assessed using a Beckman Coulter HMX analyzer, USA, with a total of 22 parameters, and microscopic slides. The biochemical parameters were measured using a Vitros 250 dry chemistry analyzer (Johnson & Johnson, USA) using the slides for multi-layer spectrophotometry measurements. We excluded patients with non-neoplastic pathologies or diseases that can induce increased serum levels of Mg and LDH. The excluded diseases included acute or chronic renal failure (CRF), ischemic heart disease, lung infarction, liver cirrhosis, acute or chronic hepatitis, massive muscle injury, megaloblastic anemia and severe syndromes that are associated with respiratory failure. Before receiving specific treatments, all patients were diagnosed at the Oncology Institute of the Fundeni Hospital in Bucharest. The physicians from the county hospital had prescribed to patients only the cancer therapy recommended by the Oncology Institute. Among the patients, 8 patients were diagnosed with lung cancer, 18 patients were diagnosed with breast cancer, 19 patients were diagnosed with genital cancer, 23 patients were diagnosed with colorectal cancer, 5 patients were diagnosed with chronic lymphocytic leukemia (CLL), 1 patient was diagnosed with acute promyelocytic leukemia (LAM-3) and 1 patient was diagnosed with chronic monocytic leukemia (CMoL). The complete blood count, blood biochemistry assays, chest and whole body radiography, echocardiography and thoracic ultrasound and/or abdominal computed tomography (CT) scans were performed for each patient to establish the type of cancer. The May-Grunwald-Giemsa method was used to determine the microscopic appearance of peripheral blood lymphocytes from patients with incipient leukemia who had not received prior treatment or a hematopoietic stem cell transplant (HSCT). Morphologically, in B-cell CLL, the cells resembled normal clonal B cells that had arrested during B cell differentiation between the pre-B cell and mature B cell stages. An initial panel of monoclonal antibodies was used to determine the immune phenotypes of the subgroups of differentiated T cells and B cells. Activated B lymphocytes in CLL patients were defined as CD5+/CD19+ cells that expressed CD23 and/or CD38 as surface markers. Activated T cells in patients with T-cell CLL were identified using CD7, CD5, CD3, CD2, CD4, CD8, and CD45 RO. The sample stability was maximal at one hour at 15-25°, in conformity with the conditions of the delivery of samples for the primary sample collection, following the instructions of the manufacturer and respecting the Procedures of Collection of Diagnostic Blood Specimens by Venipuncture, NCCLS Document H4-A3 Wayne, PA: NCCLS; 1991. We excluded samples from the study based on the following criteria: an icteric index > 65 for conjugated bilirubin and an icteric index > 37 for un-conjugated bilirubin, hemolysis with an H index > 400, turbidity for triglycerides > 300 mg/dl and serum containing para-proteins (multiple myeloma). The diagnosis of LAM-3 was made based on blood smears, the examination of bone marrow (BM) aspirates, the evaluation of promyeloblasts (greater than 30% in BM), and the presence of a specific immune phenotype. Immunocytochemical detection was performed to confirm the diagnosis of LAM-3 using FAR Leukemia kits (Italy), and there were positive results for the peroxidase reaction for promyelocytes, myelocytes, granulocytes, and peripheral blood cells (POX+) and negative results for the peroxidase reaction for the blast cells. We performed the leukocyte alkaline phosphatase reaction using a SIGMA kit (www.sigmaaldrich.com) to determine the neutrophil alkaline phosphatase (NAP) levels in granulocytes (negative or low values in LAM-3) and to evaluate the alpha-naphthyl-esterase reaction in monocytes cells (positive results indicate CMoL).

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