Quantitative phosphorylation analysis.

<p>Parental (GK1C and GK3C; red histograms) or imatinib-resistant GIST cell lines (GK1C-IR and GK3C-IR, blue histograms) were fixed and stained with anti phospho-KIT (Tyr719), anti phospho-PDGFRA (Tyr754), anti phospho-SRC (Tyr416), anti phospho-AKT (Ser473) and anti phospho-ERK1/2 (Thr202/Tyr204). Finally, cells were detected with Alexa Fluor 488 donkey anti-rabbit IgG antibody (Isotype control was reacted only with the secondary antibody). The MFI (mean of fluorescence intensity) values were calculated by FlowJo. GK1C: p-KIT = 3.21, p-PDGFRA = 10.3, p-SRC = 7.19, p-AKT = 20.3, p-ERK1/2 = 37.8. GK1C-IR: p-KIT = 3.30, p-PDGFRA = 12.8, p-SRC = 9.35, p-AKT = 20.5, p-ERK1/2 = 94.4. GK3C: p-KIT = 2.65, p-PDGFRA = 7.29, p-SRC = 5.35, p-AKT = 19.5, p-ERK1/2 = 32.2. GK3C-IR: p-KIT = 3.89, p-PDGFRA = 9.82, p-SRC = 8.31, p-AKT = 21.3, p-ERK1/2 = 115.</p

Antitumor activity of nilotinib on GIST and imatinib-resistant GIST cells.

<p>Cells were maintained in supplemented medium for 12 h, and then incubated with nilotinib (0∼100 µM) for 72 h. Cell viability was determined by comparing treated cells with the untreated control. Data are means of triplicates from a representative experiment.</p

Nilotinib antitumor activity in GIST xenograft models.

<p>(A) Immunohistochemistry staining for KIT in xenograft lines established from human GISTs: GK1X, GK2X and GK3X. (B) Tumor tissue fragments (∼5 mm³) were transplanted s.c. into the backs of BALB/cSlc-<i>nu/nu</i> mice that were randomized into 3 groups (n = 6–8). Doses of 40 mg/kg/day of imatinib, nilotinib or pure water (control) were administered by oral gavage daily for 28 days. Tumor size was measured every two to three days. (C) Tumor growth inhibition (TGI) on the day of evaluation was calculated as the ratio of tumor volume on the evaluation day to that on day 1.</p

Establishment of imatinib-resistant GIST cell lines.

<p>(A, B) Immunohistochemical assay of KIT expression in GK1C-IR and GK3C-IR as determined by staining with DAB (magnification, 400x). (C, D) GK1C and GK1C-IR cells, GK3C and GK3C-IR cells, 2.5×10³ cells (per well) were seeded into 96-well microplates in triplicate 12 h before treatment, and then exposed to different concentrations (0∼100 µM) of imatinib for 72 h. The percentage of cellular proliferation was gauged using the WST-8 method. Imatinib-resistant (IR) cells showed resistance to imatinib with IC₅₀ of 11.74±0.17 µM (<i>p<0.001</i>) or 41.37±1.07 µM (<i>p<0.001</i>). Data are presented as means ± SD and evaluated using Student's <i>t</i> test.</p

Additional file 1 of Using a multistep approach with multidisciplinary team to increase the diagnosis rate of Lynch syndrome-associated colorectal cancer after universal screening: a single-center study in Japan

Supplementary Material

Additional file 1 of Comprehensive evaluation of three-dimensional anatomy of perigastric vessels using enhanced multidetector-row computed tomography

Additional file 1: Fig. S1. Branching patterns of the celiac artery and the left gastric artery (LGA). Fig. S2. Running aspects of the hepatic artery relative to the portal vein (PV)

Additional file 1 of Pan-cancer assessment of antineoplastic therapy-induced interstitial lung disease in patients receiving subsequent therapy immediately following immune checkpoint blockade therapy

Additional file 1: Figure S1. Chest CT images showing preexisting interstitial lung disease (ILD) and drug-induced ILD (DIILD) at the post-ICI setting. Each case number corresponds to that in Table S2. In case 11 (a man with non-small cell lung cancer), CT before initiation of docetaxel therapy following prior durvalumab monotherapy showed localized subpleural reticulation in the lower right lobe (a). CT at the onset of DIILD demonstrated new diffuse ground-glass opacity (GGO) (b). In case 12 (a man with bladder cancer), CT before initiation of enfortumab vedotin therapy following prior pembrolizumab monotherapy showed bilateral peripheral linear shadows with slight GGO (c). CT at the time of DIILD diagnosis showed extensive bilateral areas of GGO and airspace consolidation with traction bronchiectasis (d). In case 14 (a man with esophageal cancer), CT before initiation of docetaxel therapy following prior nivolumab monotherapy showed slight subpleural reticulation and GGO with interlobular septal thickening in the right lower lobe (e). CT image at the onset of DIILD demonstrated multifocal patchy alveolar opacities (f)