phosphocreatine and Urinary-Bladder-Neoplasms

Urothelial bladder cancer (UBC) is one of the cancers with the highest mortality rate and prevalence worldwide; however, the clinical management of the disease remains challenging. Metabolomics has emerged as a powerful tool with beneficial applications in cancer biology and thus can provide new insights on the underlying mechanisms of UBC progression and/or reveal novel diagnostic and therapeutic schemes.. A collection of four human UBC cell lines that critically reflect the different malignancy grades of UBC was employed; RT4 (grade I), RT112 (grade II), T24 (grade III), and TCCSUP (grade IV). They were examined using Nuclear Magnetic Resonance, Mass Spectrometry, and advanced statistical approaches, with the goal of creating new metabolic profiles that are mechanistically associated with UBC progression toward metastasis.. Distinct metabolic profiles were observed for each cell line group, with T24 (grade III) cells exhibiting the most abundant metabolite contents. AMP and creatine phosphate were highly increased in the T24 cell line compared to the RT4 (grade I) cell line, indicating the major energetic transformation to which UBC cells are being subjected during metastasis. Thymosin. The present study unveils a novel and putatively druggable metabolic signature that holds strong promise for early diagnosis and the successful chemotherapy of UBC disease.

Topics: Adenosine Monophosphate; Biomarkers, Tumor; Carcinoma, Transitional Cell; Cell Line, Tumor; Disease Progression; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolic Networks and Pathways; Metabolomics; Neoplasm Grading; Phosphocreatine; Thymosin; Urinary Bladder Neoplasms

The effects of local irradiation and intraperitoneal injection of cisplatinum (CDDP) and VP-16 were examined in the sequential 31P magnetic resonance spectroscopy (MRS) in testicular cancer (TC-1) and bladder tumor (BT-8) of human origin, serially transplanted in nude mice. In the early phase of tumor growth, high-energy phosphate metabolites such as phosphocreatinine (PCr), adenosine triphosphate (ATP) and phosphomonoester (PME) were detected in both grafted tumors. However, the relative value of inorganic phosphate (Pi) to PCr increased with the growth of the tumor. Irradiation had the most pronounced effect to inhibit growth, followed by CDDP in both strains. However, growth inhibition was not observed in the VP-16 group. The effect of irradiation on the tumor histology was severely expressed in the nucleus and cytoplasm on the 4th to 7th day. The high PCr/Pi ratio during 2 to 14 days after irradiation suggested reoxygenation in the tumors with a high hypoxic cell fraction. In the CDDP and VP-16 groups, without histological change, the changes of PCr and Pi were milder than that in the irradiation group. Thus the spectroscopic analysis is presumably expected to give us an earlier and more accurate information on the tumor than the conventional parameters.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Combined Chemotherapy Protocols; Humans; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Phosphocreatine; Phosphorus Radioisotopes; Testicular Neoplasms; Urinary Bladder Neoplasms