ABSTRACT
Bladder cancer (BCa) is a prevalent disease with a high risk of aggressive recurrence in T1-stage patients. Despite the efforts to anticipate recurrence, a reliable method has yet to be developed. In this work, we employed high-resolution mass spectrometry to compare the urinary proteome of T1-stage BCa patients with recurring versus non-recurring disease to uncover actionable clinical information predicting recurrence. All patients were diagnosed with T1-stage bladder cancer between the ages of 51 and 91, and urine samples were collected before medical intervention. Our results suggest that the urinary myeloperoxidase to cubilin ratio could be used as a new tool for predicting recurrence and that dysregulation of the inflammatory and immune systems may be a key driver of disease worsening. Furthermore, we identified neutrophil degranulation and neutrophil extracellular traps (NETs) as key pathways in the progression of T1-stage BCa. We propose that proteomics follow-up of the inflammatory and immune systems may be useful for monitoring the effectiveness of therapy. SIGNIFICANCE: This article describes how proteomics can be used to characterize tumor aggressiveness in patients with the same diagnosis of bladder cancer (BCa). LC-MS/MS in combination with label free quantification (LFQ) were used to explore potential protein and pathway level changes related to the aggressiveness of the disease in 13 and 17 recurring and non-recurring T1 stage BCa patients. We have shown that the MPO/CUBN protein ratio is a candidate for a urine prognosis tool in BCa. Furthermore, we identify dysregulation of inflammation process as a driver for BCa recurrence and progression. Moreover, we propose using proteomics to track the effectiveness of therapy in the inflammatory and immune systems.
Subject(s)
Tandem Mass Spectrometry , Urinary Bladder Neoplasms , Humans , Middle Aged , Aged , Aged, 80 and over , Chromatography, Liquid , Follow-Up Studies , Urinary Bladder Neoplasms/diagnosis , Prognosis , Biomarkers, TumorABSTRACT
OBJECTIVE: To describe a case of marijuana-induced delirium and the techniques used to detect psychoactive agents and metabolites in urine. METHODS: A case of delirium following involuntary ingestion of cannabis is described. A urine sample was analyzed applying various chemical procedures, using high-resolution gas chromatography coupled with mass spectrometry technique. 11-Nor-delta9-tetrahydrocannabinol-9-carboxylic acid was quantified by the methodology for steroids and cannabis. RESULTS: A 26-year-old man was hospitalized with severe agitation and psychotic behavior 36 hours after suspected involuntary ingestion of cannabis contained in a brigadeiro, a typical Brazilian cookie, consumed during a party. Treatment with neuroleptics resulted in complete regression of the symptoms over 2 weeks. The urine sample revealed marijuana ingestion, demonstrated by the presence of its metabolite, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in high concentration. No other investigated substance was found in the patient's urine. CONCLUSION: Severe delirium can follow oral ingestion of cannabis integrated into homemade cookies.
Subject(s)
Cacao , Cannabis/toxicity , Delirium/chemically induced , Food Contamination , Psychoses, Substance-Induced/etiology , Adult , Delirium/diagnosis , Diagnosis, Differential , Dronabinol/analogs & derivatives , Dronabinol/urine , Food Contamination/analysis , Humans , Male , Metabolic Clearance Rate/physiology , Psychoses, Substance-Induced/diagnosisABSTRACT
Erythropoietin is an endogenous hormone of glicoproteic nature secreted by the kidneys and is the main regulator of the erythropoiesis. An alteration in its production generates a disturbance in the plasmatic concentration giving rise to several types of pathologies related to the hematopoietic system. The recombinant forms of erythropoietin have indiscriminately been used by athletes, mainly in endurance sports, by increasing the erythrocytes concentration, generating a better delivery of oxygen to the muscle tissue. The administration of recombinant erythropoietin was prohibited by the International Olympic Committee and its use considered as doping. This review has the intention to describe the physical, biological and pharmacokinetic properties of the endogenous erythropoietin, as well as its recombinant form, describing also its use in sports and the process of searching methodologies for its detection in doping control
