Additional file 1: Fig. S1. of Predictive value of C-reactive protein in patients treated with sunitinib for metastatic clear cell renal cell carcinoma

CONSORT 2010 Flow Diagram. (DOCX 36 kb

Additional file 4: Table S3. of Predictive value of C-reactive protein in patients treated with sunitinib for metastatic clear cell renal cell carcinoma

Adverse effects. (DOCX 20 kb

Study flow diagram.

<p>Between April 2005 and August 2009, 52 patients with metastatic melanoma were screened. Thirty-five of those patients were eligible according to inclusion criteria and received the study drug.</p

Baseline Demographic and Clinical Characteristics of Patients.

<p>Abbreviations: LDH, lactate dehydrogenase; ULN, upper limit of normal; WHO, World Health Organization.</p

Patterns of response to treatment with bevacizumab monotherapy in metastatic malignant melanoma patients.

<p>Panel A shows the best overall response for 32 patients who had undergone at least one tumor assessment measured as the change from baseline in the sum of the largest diameters of each target lesion. Three patients progressed clinically and/or biochemically before first tumor assessment, and are not shown. Negative values indicate tumor shrinkage, and the dashed lines indicate the threshold for a partial response (PR) and progressive disease (PD), respectively. Panel B shows the duration and characteristics of the responses in each patient.</p

Computed tomography showing partial responses in three different patients at baseline and at 12 months.

<p>Panel A shows ovarian metastases in a 43 years old woman. Panel B shows lung metastases in a 50 years old man. Panel C shows liver metastases and pleural effusion (*) in a 70 years old man. Arrows show the largest diameter of the lesions.</p

Kaplan Meyer plots of progression free survival (PFS) (A) and overall survival (OS) (B) in 35 metastatic melanoma patients treated with bevacizumab monotherapy.

<p>Early hypertension (EH) was significantly associated with PFS (C) and OS (D).</p

3‑(3,4-Dihydroisoquinolin-2(1<i>H</i>)‑ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3

A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2­(1H)-ylsulfonyl)­benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of “reverse sulfonamides” showed a 12-fold preference for the <i>R</i> stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay