glutaminase and Osteosarcoma

We examined the clinical significance of neoadjuvant chemotherapy (NACT) in limb salvage treatment of osteosarcoma and its effect on the Glutaminase 1 gene (GLS1) expression.. 278 patients admitted to Qianfoshan Hospital Affiliated to Shandong University with osteosarcoma were randomly divided into the study group and the control group. Patients in the study group had 3-4 courses of cisplatin, ifosfamide, and adriamycin (DIA) chemotherapy before surgical excision, while no chemotherapy was used in the control group before the surgery.. GLS1 expression in the study group decreased, the difference showed statistical significance compared with that of the control group (p<0.05). The median survival time of the study group was 48.4±19.7 months while in the control group was 42.4±11.2. The overall survival time of study group was 58.5±15.2 months, which was significantly higher than control 49.4±10.7 (p<0.05). The higher GLS1 expression in osteosarcoma was, the shorter the patients' survival time would be.. Neoadjuvant chemotherapy performed before surgery could significantly decrease the GLS1 expression in osteosarcoma, effectively improving limb salvage treatment of osteosarcoma. The higher the GLS1 expression was, the shorter the patients' survival time would be.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Chemotherapy, Adjuvant; Child; China; Cisplatin; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Glutaminase; Humans; Ifosfamide; Limb Salvage; Male; Middle Aged; Neoadjuvant Therapy; Orthopedic Procedures; Osteosarcoma; Risk Factors; Time Factors; Young Adult

Profiling the endogenous tissue metabolites with spatial features is significant for our understanding of molecular histology, and provides an insightful way to uncover the complex associations between tissue metabolic response and external stimuli. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an effective molecular imaging technology to illustrate the spatial locations of molecules in tissue. However, due to the limited sensitivity and the presence of multiple matrix-related ions, it is still challenging to globally image the small molecule metabolites (SMMs) using MALDI, especially for those low-content functional ones. Here, a simple acetone washing method was developed to improve the sensitivity of MALDI-MS for imaging SMMs. After immersing in acetone and shaken for 15 min, key functional SMMs were well-visualized with significantly enhanced ion intensities. In addition to lipids, more than 160 SMM ions, including polyamines, cholines, carnitines, amino acids, nitrogenous bases, nucleosides, carbohydrates, organic acids, vitamins were imaged. The acetone washes-based MALDI-MSI was then applied to profile the metabolic alternations that occurred in osteosarcoma, and the abnormally altered SMMs and lipids were clearly visualized. Moreover, with the protection of acetone against tissue antigenicity, we successfully characterized the expression of three metabolites-related enzymes, fatty acid synthase (FASN), glutaminase (GLS), and cytosolic phospholipase A2 (cPLA2) in osteosarcoma. The spatially-resolved metabolite and corresponding enzyme information reveals what occured in osteosarcoma at the molecular level, providing new insights into the understanding of tumour metabolic reprogramming.

Topics: Acetone; Animals; Disease Models, Animal; Fatty Acid Synthase, Type I; Glutaminase; Histocytological Preparation Techniques; Humans; Immersion; Mice; Molecular Imaging; Osteosarcoma; Phospholipases A2, Cytosolic; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Topics: Adenocarcinoma; Adenoma; Animals; Carcinoma 256, Walker; Carcinoma, Squamous Cell; Fibrosarcoma; Glutaminase; Growth; Mammary Neoplasms, Experimental; Mathematics; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Osteosarcoma; Rats; Time Factors