Fatty Acid Patterns Detected By Ambient Ionization Mass Spectrometry in Canine Invasive Urothelial Carcinoma From Dogs of Different Breeds.

BACKGROUND: In early work ambient ionization mass spectrometry (MS) revealed lipid patterns distinguishing muscle invasive bladder cancer (invasive urothelial carcinoma, InvUC) from normal urothelium. A new ambient ionization MS approach, touch spray MS (TS-MS) can rapidly generate mass spectra in real time, potentially in a point-of-care setting. A tissue sample removed from a patient is touched by a probe, and mass spectra generated within seconds. OBJECTIVE: To validate TS-MS methods using specimens from naturally-occurring InvUC in dogs where the cancer closely mimics the human condition, and to demonstrate proof-of-concept that TS-MS can elucidate lipid patterns distinguishing InvUC from normal urothelium. METHODS: Samples of normal urothelium and InvUC from dogs of several breeds were analyzed by TS-MS with correlative histopathology across each sample. Results were compared to those obtained with desorption electrospray ionization mass spectrometry (DESI-MS), a more traditional method. Data were analyzed by Principal Component Analysis and Linear Discriminant Analysis. RESULTS: Lipid patterns identified by TS-MS, as well as by DESI-MS, differed between InvUC and normal urothelium with m/z 281.5 (oleic acid) and m/z 563.5 (oleic acid dimer) substantially contributing to the differences. Using histologic diagnosis as the gold standard, TS-MS had a global prediction rate of 93%. CONCLUSIONS: TS-MS can be used to identify lipid patterns that differentiate canine InvUC from normal urothelium. Optimization of TS-MS could lead to a point-of-care approach to distinguish cancer from normal in ex vivo tissues in real time, and to define biochemical processes leading to cancer development and progression.

Feasibility of desorption electrospray ionization mass spectrometry for diagnosis of oral tongue squamous cell carcinoma.

RATIONALE: Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated utility in differentiating tumor from adjacent normal tissue in both urologic and neurosurgical specimens. We sought to evaluate if this technique had similar accuracy in differentiating oral tongue squamous cell carcinoma (SCC) from adjacent normal epithelium due to current issues with late diagnosis of SCC in advanced stages. METHODS: Fresh frozen samples of SCC and adjacent normal tissue were obtained by surgical resection. Resections were analyzed using DESI-MS sometimes by a blinded technologist. Normative spectra were obtained for separate regions containing SCC or adjacent normal epithelium. Principal Component Analysis and Linear Discriminant Analysis (PCA-LDA) of spectra were used to predict SCC versus normal tongue epithelium. Predictions were compared with pathology to assess accuracy in differentiating oral SCC from adjacent normal tissue. RESULTS: Initial PCA score and loading plots showed clear separation of SCC and normal epithelial tissue using DESI-MS. PCA-LDA resulted in accuracy rates of 95% for SCC versus normal and 93% for SCC, adjacent normal and normal. Additional samples were blindly analyzed with PCA-LDA pixel-by-pixel predicted classifications as SCC or normal tongue epithelial tissue and compared against histopathology. The m/z 700-900 prediction model showed a 91% accuracy rate. CONCLUSIONS: DESI-MS accurately differentiated oral SCC from adjacent normal epithelium. Classification of all typical tissue types and pixel predictions with additional classifications should increase confidence in the validation model.

Stereocartography: a computational mapping technique that can locate regions of maximum stereoinduction around chiral catalysts.

A hypothesis concerning asymmetric induction by chiral catalysts is posited, tested, and found to be valid. The hypothesis states that chiral catalysts that are efficient at inducing asymmetry will have their region of maximum stereoinduction spatially congruent with the site of chemistry but inefficient catalysts will not. A simple mapping strategy (stereocartography) is used to assess where the region of maximum stereoinduction is located around a given catalyst. The protocol compares interaction energies between mirror image probes at each point in space around the catalyst being considered. The probes are models of the actual transition states of the reaction being catalyzed by a particular catalyst. The hypothesis was tested on three Diels-Alder reactions. Seventeen of the eighteen catalysts conform to the hypothesis. The idea of using this as a catalyst design tool is presented.