Additional file 1: of Medullary carcinoma of the pancreas radiologically followed up as a cystic lesion for 9Â years: a case report and review of the literature

Positron emission tomography (PET). The maximum standardized uptake value of the preoperative lesion was 6.8 (arrows). (PPTX 120 kb

Additional file 2: of Medullary carcinoma of the pancreas radiologically followed up as a cystic lesion for 9Â years: a case report and review of the literature

Immunohistochemical staining. The tumor was positive for cytokeratin (CK)-7 and CK-20, and focally positive for mucin (MUC) 5 AC and MUC6. The tumor was negative for MUC2 and caudal-type homeobox (CDX) 2. (PPTX 9523 kb

Recurrence rate of PDOX in each treatment group.

<p>* p = 0.041, compared to FGS only.</p><p>Recurrence rate of PDOX in each treatment group.</p

Representative gross and histological images of excised tumors in each treatment group.

<p>Left panels of (A) and (B) indicate bright field (BF) images and right panels indicate fluorescence images for DyLight 650 (650). Histopathological response to GEM treatment was defined according to Evans’s grading scheme. The tumors without GEM treatment (FGS only) were comprised of viable cancer cells that formed glandular structures and judged as Grade I (C). In the tumors with GEM treatment, over 50% of cancer cells were dead and replaced by necrotic tissue or stromal cells (D). Treatment efficacy of GEM on the pancreatic cancer PDOX was judged as grade IIb - III (D). Fluorescence decreased in some areas of the tumor treated with GEM, but was sufficient for FGS (B). Scale bars: 5 mm (A and B), 250 µm (C and D).</p

Antibody labelling of the pancreatic cancer patient derived orthotopic xenograft.

<p>The patient’s pancreatic cancer was diagnosed as moderately differentiated adenocarcinoma with H&E staining (A). The tumor was strongly stained with anti-CA19-9 antibody (B), whereas the signal was very weak with anti-CEA antibody (C). Scale bars: 100 µm. (D and E) Whole body images of a subcutaneous tumor in nude mice labeled with anti-CA19-9- or anti-CEA-conjugated DyLight 650. Fifty µg anti-CA19-9 DyLight 650 or anti-CEA DyLight 650 was injected in the tail vain of the mice with subcutaneous tumors. Twenty-four hours later, whole body images were taken with the OV100 (Olympus). Yellow arrowheads indicate subcutaneous tumors. The subcutaneous tumors were brightly labeled with anti-CA19-9 DyLight 650 (D), whereas, the fluorescence signal from the tumor labeled with anti-CEA DyLight 650 was very weak (E). Scale bars: 10 mm.</p

Experimental schema and FGS imaging system.

<p>(A) Schema of the experimental design. After confirmation of tumor growth, the PDOXs were randomized to 4 groups: BLS only; BLS+NAC; FGS only; or FGS+NAC. Each treatment arm involved 8 tumor-bearing mice. The mice randomized to the NAC groups were treated with GEM (80 mg/kg) on day 8, 15 and 22. All animals underwent surgery on day 29. BLS was performed under standard bright-field using the MVX10 microscope. Fifty µg of anti-CA19-9 antibody conjugated with DyLight 650 was injected in the tail vain of mice with tumors in the FGS group 24 hours before surgery. FGS was performed using the MINI MAGLITE LED PRO flash light (MAG INSTRUMENT, Ontario, CA, USA) with excitation filter ET640/30X (Chroma Technology Corporation, Bellows Falls, VT, USA) and a Canon EOS 60D digital camera with an EF–S18–55 IS lens (Canon, Tokyo, Japan) and emission filter HQ700/75M-HCAR (Chroma Technology Corporation) under fluorescence navigation (B). Twelve weeks after surgery, animals underwent laparotomy, and the tumors were imaged, weighed and harvested for analysis. Scale bars: 2 cm (filters) and 5 cm (flash light).</p

Recurrent tumor weights for each experimental group.

<p>(A) Recurrent tumor weight in the BLS-only; BLS+NAC; FGS-only; and FGS+NAC treatment groups. The average local recurrent tumor weight for FGS-only treatment was significantly less than for BLS-only treatment (p = 0.0041). The average local recurrent tumor weight for FGS+NAC treatment was also significantly less than for BLS+NAC treatment (p = 0.008). The average metastatic recurrent tumor weight for FGS+NAC treatment was significantly less than for BLS+NAC treatment (p = 0.001). FGS+NAC treatment reduced recurrence rate significantly compared to FGS-only treatment (p = 0.041) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114310#pone-0114310-t001" target="_blank">Table 1</a>). FGS+NAC treatment tended to reduce the metastatic recurrent tumor weight compared to FGS-only treatment (p = 0.059).</p

Representative images during FGS with or without NAC.

<p>Upper panels indicate bright field (BF) images and lower panels indicate fluorescence images for DyLight 650 (650). The fluorescence in the tumors treated with GEM (B) decreased compared to untreated tumors (A), but were still clearly detected. Scale bars: 10 mm.</p

ZA inhibits Edu-macrophages and tumor progression induced by Edu macrophages in the orthotopic XPAI pancreatic cancer mouse model.

<p>(<b>A</b>) Representative fluorescence images of Edu-macrophages after ZA treatment. Scale bars: 10 µm. (<b>B</b>) Bar graphs of the number of Naïve- or Edu-macrophages after ZA treatment in vitro. The numbers of both Naïve- and Edu-macrophages treated with ZA were significantly reduced at every dose. ZA killed both Naïve and Edu in a dose-dependent manner. ** <i>P</i><0.01 (vs. control group). (<b>C</b>) Intravital imaging of XPA1-RFP tumor-bearing mice at the termination of the experiment. Scale bars: 10 mm. (<b>D</b>) The primary tumor weight of Edu-macrophage-treated mice were significantly increased compared to control or Naïve-macrophage-treated mice (control: <i>P</i> = 0.026; Naïve: <i>P</i> = 0.03, respectively). The primary tumor weight of Edu-macrophage + ZA-treated mice were significantly decreased compared to Edu-macrophage-treated mice (<i>P</i> = 0.006). * <i>P</i><0.05, ** <i>P</i><0.01. (<b>E</b>) The metastasis weight of Edu-macrophage-treated mice were significantly increased compared to control or Naïve-macrophage-treated mice (control; <i>P</i> = 0.012, Naïve; <i>P</i> = 0.015, respectively). No metastasis was detected in Edu + ZA-treated mice. There was a significant difference between Edu and Edu + ZA-treated mice (<i>P</i> = 0.025). * <i>P</i><0.05.</p

Tumor-Targeting <i>Salmonella typhimurium</i> A1-R Arrests a Chemo-Resistant Patient Soft-Tissue Sarcoma in Nude Mice

<div><p>A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) <i>Salmonella typhimurium</i> A1-R (5 × 10⁷ CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). <i>S</i>. <i>typhimurium</i> A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). <i>S</i>. <i>typhimurium</i> A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting <i>S</i>. <i>typhimurium</i> A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma.</p></div