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A, B Hemoglobin (A) and hematocrit (B) levels of healthy subjects and cachectic cancer patients presenting a body weight loss superior to 10% of initial body weight (19 healthy subjects, 17 cachectic patients). C TFR1 mRNA levels in muscle biopsies from cancer patients of late stage cachexia with at least 10% total body weight loss (19 healthy subjects, 17 cachectic patients). D Gastrocnemius weight in mice subjected to iron deprivation by feeding with an iron‐deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). E TFR1 mRNA levels in the liver of mice subjected to iron deprivation by feeding with an iron‐deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). F TFR1 mRNA levels in the gastrocnemius of mice subjected to iron deprivation by feeding with an iron‐ deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). G Cross‐sectional area of skeletal muscle fibers transfected with shSCR (scramble) and shTFR1 ( n = 3–4) and representative picture of shTFR1 transfected fibers. Scale bar = 50 µm. H Cross‐sectional area of skeletal muscle fibers transfected with TFR‐pHuji ( n = 4) and representative picture of TFR‐pHuji transfected fibers. Scale bar = 50 µm. I, J Diameter of TFR1 (I) or NCOA4 (J) knocked down C2C12 myotubes at day 3 post‐transfection ( n = 7 and n = 3 respectively). K Diameter of C2C12 myotubes after 48 h treatment with Deferoxamine (DFO), <t>bathophenanthroline</t> disulfonate (BPS), or apo‐transferrin (Apo‐Tf). L Representative pictures and diameter measurements of human myoblast‐derived myotubes after 48 h treatment with DFO ( n = 3). Scale bar = 50 µm. Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two‐tailed Student’s t ‐test. Data are mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001. Source data are available online for this figure.
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A, B Hemoglobin (A) and hematocrit (B) levels of healthy subjects and cachectic cancer patients presenting a body weight loss superior to 10% of initial body weight (19 healthy subjects, 17 cachectic patients). C TFR1 mRNA levels in muscle biopsies from cancer patients of late stage cachexia with at least 10% total body weight loss (19 healthy subjects, 17 cachectic patients). D Gastrocnemius weight in mice subjected to iron deprivation by feeding with an iron‐deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). E TFR1 mRNA levels in the liver of mice subjected to iron deprivation by feeding with an iron‐deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). F TFR1 mRNA levels in the gastrocnemius of mice subjected to iron deprivation by feeding with an iron‐ deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). G Cross‐sectional area of skeletal muscle fibers transfected with shSCR (scramble) and shTFR1 ( n = 3–4) and representative picture of shTFR1 transfected fibers. Scale bar = 50 µm. H Cross‐sectional area of skeletal muscle fibers transfected with TFR‐pHuji ( n = 4) and representative picture of TFR‐pHuji transfected fibers. Scale bar = 50 µm. I, J Diameter of TFR1 (I) or NCOA4 (J) knocked down C2C12 myotubes at day 3 post‐transfection ( n = 7 and n = 3 respectively). K Diameter of C2C12 myotubes after 48 h treatment with Deferoxamine (DFO), bathophenanthroline disulfonate (BPS), or apo‐transferrin (Apo‐Tf). L Representative pictures and diameter measurements of human myoblast‐derived myotubes after 48 h treatment with DFO ( n = 3). Scale bar = 50 µm. Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two‐tailed Student’s t ‐test. Data are mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001. Source data are available online for this figure.

Journal: EMBO Reports

Article Title: Iron supplementation is sufficient to rescue skeletal muscle mass and function in cancer cachexia

doi: 10.15252/embr.202153746

Figure Lengend Snippet: A, B Hemoglobin (A) and hematocrit (B) levels of healthy subjects and cachectic cancer patients presenting a body weight loss superior to 10% of initial body weight (19 healthy subjects, 17 cachectic patients). C TFR1 mRNA levels in muscle biopsies from cancer patients of late stage cachexia with at least 10% total body weight loss (19 healthy subjects, 17 cachectic patients). D Gastrocnemius weight in mice subjected to iron deprivation by feeding with an iron‐deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). E TFR1 mRNA levels in the liver of mice subjected to iron deprivation by feeding with an iron‐deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). F TFR1 mRNA levels in the gastrocnemius of mice subjected to iron deprivation by feeding with an iron‐ deficient diet (IDD) combined to a phlebotomy (PHL) ( n = 5–6). G Cross‐sectional area of skeletal muscle fibers transfected with shSCR (scramble) and shTFR1 ( n = 3–4) and representative picture of shTFR1 transfected fibers. Scale bar = 50 µm. H Cross‐sectional area of skeletal muscle fibers transfected with TFR‐pHuji ( n = 4) and representative picture of TFR‐pHuji transfected fibers. Scale bar = 50 µm. I, J Diameter of TFR1 (I) or NCOA4 (J) knocked down C2C12 myotubes at day 3 post‐transfection ( n = 7 and n = 3 respectively). K Diameter of C2C12 myotubes after 48 h treatment with Deferoxamine (DFO), bathophenanthroline disulfonate (BPS), or apo‐transferrin (Apo‐Tf). L Representative pictures and diameter measurements of human myoblast‐derived myotubes after 48 h treatment with DFO ( n = 3). Scale bar = 50 µm. Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two‐tailed Student’s t ‐test. Data are mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001. Source data are available online for this figure.

Article Snippet: Deferoxamine (DFO, Sigma D9533) and bathophenanthroline disulfonic acid (BPS, Sigma 146617) were used at 100 µM.

Techniques: Transfection, Derivative Assay, Two Tailed Test