Bioactive Sphingolipids and metabolizing enzymes in patients with benign prostate hyperplasia and malignant prostate cancer

number: 
3858
إنجليزية
department: 
Degree: 
Author: 
Raghdah Abdul-Monaam Razoqi
Supervisor: 
Dr. Raid J. Mohamed Lecturer
Dr. Usama S. Al-Nasiri Professor
year: 
2017

       Bioactive Sphingolipids an important molecules of structural and signaling lipids. In this study was highlight on new biomarkers uses to investigate prostate cancer by using new method HPLC fluorescence detector to measure concentration and activity enzymes sphingosine-1-phosphate lyase enzyme (SPL) and Acid Ceramidase enzyme (AC) by used new material (BODIPY) aromatic structural is binding with enzymes and give fluorophore product sensitive by HPLC fluorescence detector in patients have BPH and PC in serum and tissue and comparing with healthy men as (control). Eliza method was used to measured sphingosine-1-phosphate and Ceramide in patients (BPH and PC) in serum and tissue and controls in serum. Sphingolipids metabolites pathological processes, are astablished regulators of myriad cellular and sphingolipids research is intricate due to the role of these molecules in vastly different biologics, interconnected metabolic pathways and structural properties. Ceramide and sphingosine-1-phosphate (S1P), SGPL and AC have been defined as reciprocal regulators of cellular fate, and not surprisingly have been targeted for their role in cancer and their therapeutic potential, sphingolipid metabolic enzymes and lipids are metabolically interconnected and highlight recent findings to support the reciprocal role of Ceramide and S1P in cellular processes and in cancer. Studies show increase levels markers in serum and tissue in BPH and PC with healthy men and different activity Km and V max in AC and SPL between healthy, BPH and PC patients and this reaction was noncompetitive inhibition with enzyme because V max was change and Km was not change in all cases these results were accepted with studies in  America and Spain.

Aim of study 

  The main aim of this study is found a new sensitive and specific bio markers for diagnosis prostatic cancer because PSA levels test may give false-positive or false-negative results. False-positive test result occurs when level of PSA of man PSA is elevated but no cancer is actually present. False-positive test result may create anxiety for a man and his family and lead to additional medical procedures, such as a prostate biopsy, that can be harmful. Possible side effects of biopsies include serious infections, pain, and bleeding, most men with an elevated PSA level turn out not to have prostate cancer, only about 25 percent of men who have a prostate biopsy due to an elevated PSA level actually have prostate cancer .A false-negative test result occurs when a level of PSA of man is low even though actually has prostate cancer. False-negative test results may give a man false assurance that he does not have cancer, when he may in fact have a cancer that requires treatment. and other goals of conducting this study are:

1-      To measure activity of Acid ceramidase and Sphingosine-1-Phospate Lyase in sera and prostate tissue of patients with benign prostatic hyperplasia and prostate cancer and compare these activities of enzymes with normal controls.

2- To determine the concentration of bioactive Sphingolipids Ceramide and  Sphingosine-1- phosphate in tissues and sera of the patients and control.

3- To correlate the level of bioactive lipids with serum PSA concentration to detect their use as additional biomarker for diagnosis and follow up of patient with prostate cancer.

Methods: A case-control study design was employed in this study. On a total of 30 patients with confirmed PC, 30 patients with BPH and age matched 30 healthy men. Prostate tissue samples were obtained for patients were serum and urine samples were collected for patients and controls. Enzyme linked immune assay (Elisa) was used to measure  S1P and Ceramide concentration  in serum and tissue, while HPLC fluorescence detector was used to estimate activities of SPL and AC and measured Km and V max. Urine and serum samples were undergone biochemistry analysis. HbA1c was used to measure cumulative sugar for three groups. Protein in tissue was measure by brad ford method to PC and BPH patients.

Results: The results showed that increase levels of Sphingosine 1 phosphate lyase and Acid ceramidase in serum and tissue in BPH and Malignant cancer in men these levels were different result in patient were taken drugs or not and patients were taken chemotherapy or not and activity, Km and Vmax of enzyme SPL and AC were different in BPH and PC that men is inhibition enzymes was noncompetitive it had same Km but different data of control, BPH and PC men in tissue and serum.     The concentration of S1P and Ceramide were different levels with control, and high levels in patients without any drugs or chemotherapy while levels of these markers still low with patients were taken drugs or chemotherapy and level of protein in tissue were raised. Results of biochemistry analysis still normal because we take patients without any D.M., renal failure, and hypertension.