SEPT9_i1 staining in prostate cancer metastases.

<p>Metastatic prostate cancer lesions from bone marrow, lymph node and bone were immunostained with SEPT9_i1. Left panels are low (x100) magnification (LM) (scale bar 100 μm) and right panel are high (x200) magnification (HM) (scale bar 50 μm). Note high level of SEPT9_i1 staining in all metastases.</p

Correlation between "patients' characteristics" and SEPT9_i1 staining.

<p>PSA, prostate-specific antigen.</p><p>Correlation between "patients' characteristics" and SEPT9_i1 staining.</p

Characterization of SEPT9_i1 antibodies and scoring of SEPT9_i1 staining intensity.

<p>HEK-293T embryonic human kidney cells were transiently transfected with Flag-SEPT9_i1 construct or empty vector (EV). (A) Whole cellular extracts were prepared and analyzed by 4–20% SDS-PAGE and immunoblotting (IB) with antibodies to Flag (1:2000), SEPT9_i1 (1:3000), preimmune serum (1:3000) or SEPT9_i1 antibody (1:3000) pre-incubated with 10 μM of the immunogen peptide for 4 hours. (B) The same cellular extracts were subjected to immunoprecipitation (IP) using anti-Flag antibody and the immuneprecipitates were subjected to 4–15% SDS-PAGE and then immunoblotted with anti-Flag or anti-SEPT9_i1 antibodies. (C) Representative SEPT9_i1 staining in human prostate cancer specimens. Score 0: no SEPT9_i1 staining, 1: low SEPT9_i1 staining 2: medium SEPT9_i1 staining and 3: high SEPT9_i1 staining. Magnification x200, scale bar 50 μm.</p

Main characteristics of study participants.

<p>PSA, prostate-specific antigen; CI, confidence interval; NA, not available.</p><p>Main characteristics of study participants.</p

Gleason score correlation with SEPT9_i1 staining intensity.

<p>Mean SEPT9_i1 staining intensity ± SE of each Gleason score group (score 5: 3 patients, score 6: 8 patients, score 7: 19 patients, score 8: 3 patients, score 9: 6 patients and score 10: 2 patients) was calculated using either visual scoring (A) or automated image analysis with the ARIOL-SL50 system (B).</p

Biochemical profile from rats at 2, 3, 5, and 6 weeks.

<p>After 2 weeks, there was a significant increase in urea and creatinine levels, reflecting renal failure (RF). After 3 weeks, phosphate levels also increased compared with control; RF worsened in Week 5 and plateaued. As part RF, hypocalcaemia developed after 3 weeks, remaining constant. There were no significant changes in potassium, sodium, or cholesterol levels.</p><p>*<i>P</i> < 0.05 between diet groups and control group.</p><p>Biochemical profile from rats at 2, 3, 5, and 6 weeks.</p

Macrophages osteoblast markers and intracellular pathways in early phases of calcification.

<p>(A) Immunostaining of CD68 (I), osteopontin (II), and osteocalcin (III) were positive in the valve annulus (An) and leaflets (Le) after 2 weeks on the nephropathic diet. (B) Western blot analysis (n = 3 in each group) of osteocalcin, osteopontin, and Runx-2 (I), and of the ratio of phosphorylated ERK to ERK-1(II). There were no changes in the expression Akt, JNK, or p38 pathways (III). Graphic presentation of Western blot analysis (IV).</p

TL-118 and Gemcitabine Drug Combination Display Therapeutic Efficacy in a MYCN Amplified Orthotopic Neuroblastoma Murine Model – Evaluation by MRI

<div><p>Neuroblastoma (NB) is the most common extra-cranial pediatric solid tumor with up to 50% of NB patients classified as having high-risk disease with poor long-term survival rates. The poor clinical outcome and aggressiveness of high-risk NB strongly correlates with enhanced angiogenesis, suggesting anti-angiogenic agents as attractive additions to the currently insufficient therapeutics. TL-118, a novel drug combination has been recently developed to inhibit tumor angiogenesis. In the current study, we used the SK-N-BE (2) cell line to generate orthotopic NB tumors in order to study the combinational therapeutic potential of TL-118 with either Gemcitabine (40 mg/kg; IP) or Retinoic acid (40 mg/kg; IP). We show that TL-118 treatment (n = 9) significantly inhibited tumor growth, increased cell apoptosis, reduced proliferation and extended mouse survival. Moreover, the reciprocal effect of TL-118 and Gemcitabine treatment (n = 10) demonstrated improved anti-tumor activity. The synergistic effect of these drugs in combination was more effective than either TL or Gemcitabine alone (n = 9), via significantly reduced cell proliferation (p<0.005), increased apoptosis (p<0.05) and significantly prolonged survival (2-fold; p<0.00001). To conclude, we demonstrate that the novel drug combination TL-118 has the ability to suppress the growth of an aggressive NB tumor. The promising results with TL-118 in this aggressive animal model may imply that this drug combination has therapeutic potential in the clinical setting.</p></div

ECM expressions.

<p>Aortic valve sections, including the annulus (An) and a leaflet (Le), from study groups before and after immunohistochemical staining. (A) Collagen 1 staining. (B) Staining of collagen 3. (C) Staining of fibronectin.</p

Treatment effect on tumor growth and mouse survival.

<p>A. Tumor volume (mm³) for each individual mouse, as measured from T₂W MRI images as a function of days post cell inoculation in control (n = 19), Gemcitabine (Gem; n = 6), TL-118^1/4 (n = 9) and TL^1/4+ Gem combination (n = 10) treated mice. The dashed line indicates the maximal survival day of the control-treated mice. The b-values represent the average exponential coefficients of each treatment group. The b-values of all the treated groups (Gem, TL^1/4 and TL^1/4+ Gem) were significantly lower compared to control (p<0.0001). B. Representative T₂W anatomical axial images of Control, Gem, TL-118^1/4 and TL^1/4+ Gem treated tumors that were acquired on the indicated days (Bar = 1 cm) C. Kaplan-Meier survival analysis for each of the treated groups (*p<0.05; **P<0.0001; ***p<0.00001 compared to control). D. Box and Whisker plots of mean calculated b-values for each treated group (black square – median; * p<0.0001).</p