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Primary data for BJC Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo


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Authors

Griffiths, JR 
Lee, Shen-Han 
McIntyre, Dominick John 
Honess, Davina Jean 
Hulikova, Alzbeta 

Description

The paper describing these data is available free of charge from https://www.nature.com/articles/s41416-018-0216-5 and readers are encouraged to download it to view the figures and full details of acquisition protocols and analysis of the data presented here.

Figure 6 sources.zip

Figure 6 plots intracellular pH (pHi) for each tumour measured by magnetic resonance spectroscopy (MRS), lactate overall measured by enzymatic methods, and models of intra/extracellular lactate distribution.

Figure 6 as png and svg files (lac_combo2.png/svg)

phi_vs_phe.csv: Experimentally measured pHi (31P MRS) and extracellular pH (pHe) values (1H MRS of ISUCA) in empty vector control EV5 and carbonic anhydrase 9 overexpressing CA9 model tumours in mice

CA9_lactate_enzymatic files - enzymatically measured lactate concentrations for tumour samples.

lactateplot.py: python code to generate the plots in Figure 6, including computing intracellular & extracellular lactate from measured total lactate, pHi and pHe, and testing normality and significance of tumour type for pHi (ns) and pHe (p0.001 Mann-Whitney test). Statistical output in laccalc_output.xlsx

Figure 5 sources.zip

Figure 5 compares pHi and pHe values for CA9 tumour measured by 1H magnetic resonance spectroscopy of ISUCA, demonstrating minimal overlap phi_vs_phe.csv: Experimentally measured pHi (31P MRS) and pHe values (1H MRS of ISUCA) in EV and CA9 tumours. EV data not plotted.

phi_vs_phe.csv: Experimentally measured pHi (31P MRS) and pHe values (1H MRS of ISUCA) in EV and CAIX/1 tumours

phi_vs_e_ca9.py: Code to generate pHi and pHe box and whisker plots from above data

Figure in multiple graphic formats

raw data for plotting Fig 2.xlsx

Figure 2 contains plots of exofacial CA and CO2 hydration rates for the model tumours in this study; the raw data are presented in this spreadsheet.

Code for 1H MRS analysis.zip

This contains a walkthrough for the spectroscopic quantitation of the 1H MRS data provided in 1H MRS data.zip, together with the python 2 code used to generate the pH colourmaps overlaid on anatomical images for Fig 4a and Supplementary Figures 1 and 2

1H MRS data.zip, 31P MRS data.zip:

All MRS and MRI data acquired from the tumours described in this work. Data were acquired on an Agilent MRI scanner with a 9.4T magnet. Each file contains one folder per tumour and a spreadsheet mapping study. MRS data are available in folders with names starting presscsi_expt_isuca for 1H chemical shift imaging MRS of ISUCA and 31Pisis for 31P single-voxel MRS of native metabolites enabling direct measurement of pHi.

Images and spectra are proprietary formats but may be read with a number of free software programs. We recommend using ImageJ or Fiji (https://fiji.sc/) for the image files (extension fdf) and jMRUI (http://www.jmrui.eu/) for the spectroscopy data. We used jMRUI for the data analysis and all quantified data are also included in these data sets. Results files are stored in the same directory with the raw data and have names ending AMARES.results. Default jMRUI parameters are provided in AMARES parameters in 1H MRS data.zip and in jMRUI parameter files in 31P MRS data.zip. Analysis procedures for spectroscopic imaging are provided in the separate file Code for 1H MRS analysis.zip; the simpler procedure for the 31P MRS analysis is provided in the file 31P Analysis walkthrough.doc in 31P MRS data.zip.

Version

Software / Usage instructions

jMRUI http://www.jmrui.eu/ python www.python.org Excel

Keywords

Carbonic anhydrase IX, Extracellular pH, Intracellular pH, ISUCA, Magnetic Resonance Spectroscopy, MRS, pH-stat, Tumour pH

Publisher

Sponsorship
Cancer Research UK (C14303/A17197)
In addition to the CRUK funding linked, we are grateful for support from the Breast Cancer Research Foundation, the Royal Society, Worldwide Cancer Research and the European Research Council (SURVIVE: 723397). J.P.-T. and S.C. received support from the Spanish Ministry of Economy and Competitiveness SAF2014-23622
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