Accumulation of the COMMD1 protein as a druggable pharmacology event to target cancer cells has not been evaluated so far in cancer animal models. We have previously demonstrated that a second-generation peptide, with cell-penetrating capacity, termed CIGB-552, was able to induce apoptosis mediated by stabilization of COMMD1. Here, we explore the antitumor effect by subcutaneous administration of CIGB-552 in a therapeutic schedule. Outstandingly, a significant delay of tumor growth was observed at 0.2 and 0.7 mg/kg (p < 0.01) or 1.4 mg/kg (p < 0.001) after CIGB-552 administration in both syngeneic murine tumors and patient-derived xenograft models. Furthermore, we evidenced that (131)I-CIGB-552 peptide was actually accumulated in the tumors after administration by subcutaneous route. A typical serine-proteases degradation pattern for CIGB-552 in BALB/c mice serum was identified. Further, biological characterization of the main metabolites of the peptide CIGB-552 suggests that the cell-penetrating capacity plays an important role in the cytotoxic activity. This report is the first in describing the antitumor effect induced by systemic administration of a peptide that targets COMMD1 for stabilization. Moreover, our data reinforce the perspectives of CIGB-552 for cancer targeted therapy.

To compare the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFG) for the detection of latent tuberculosis infection among patients with immune-mediated inflammatory diseases before antitumor necrosis factor-α therapy. A prospective study including 153 consecutive patients with rheumatoid arthritis (n = 53), psoriasis (n = 45), inflammatory bowel disease (n = 25), and spondyloarthropathy (n = 22) were included. QFG and TST were performed simultaneously. TST was positive in 43/153 (28.1 %) patients. QFG (cutoff ≥ 0.35 IU/ml) was positive in 15/153 (9.8 %) patients, and indeterminate in one (0.7 %). QFG (cutoff ≥ 0.10 IU/ml) was positive in 25/153 (16.3 %). 59.5 % of the patients were on immunosuppressive therapy at the time of testing. There was a significant difference in the rate of positive QFG between patients with and without immunosuppressive therapy after adjustment for age and gender (cutoff ≥ 0.35 IU/ml, 4.6 vs. 17.4 %; adjusted odds ratio [AOR], 0.2; 95 % confidence interval [CI], 0.06-0.8; p = 0.03 and cutoff ≥ 0.10 IU/ml, 11.2 vs. 24.2 %; AOR, 0.3; 95 % CI, 0.1-0.93; p = 0.04). Agreement between TST and QFG was 'fair' (κ = 0.354 and κ = 0.365, for cutoffs ≥ 0.35 and ≥0.10 IU/ml, respectively). Among patients without immunosuppressive therapy, the concordance between TST and QFG was 'moderate-substantial' (κ = 0.593 and κ = 0.690, for cutoffs ≥ 0.35 IU/ml and ≥0.10 IU/ml, respectively). By contrast, among patients on immunosuppressive therapy the concordance was 'poor' (κ = 0.085; κ = 0.041, respectively). Immunosuppressive therapy affects negatively QFG performance. In patients with immune-mediated inflammatory diseases, QFG may have a limited role for screening of latent tuberculosis infection.

Mycobacteria other than tuberculosis infections in patients taking various tumour necrosis factor (TNF)-a inhibitors have been reported in the literature. We describe sporotrichoid spread of Mycobacterium marinum in a man with Crohn's disease treated with infliximab. After starting ethambutol and rifampicin and discontinuing infliximab, a worsening appeared. M. marinum infection may have a potential local spread and systemic dissemination in patients treated with TNF-a inhibitors. Case reportA 32-year-old man was referred to our department because of cellulitis of the thumb on the right hand despite a course of cloxacillin and another of amoxicillin/clavulanic acid. His medical history included Crohn's disease since 1996. In September 2005, he had been started on infliximab infusions with an excellent clinical response. A tuberculin skin test performed before administration of infliximab was negative and a chest X-ray revealed no evidence of active or prior tuberculosis. After 6 months, the infliximab infusion was stopped. In September 2007, his disease worsened despite maintaining a background therapy that included prednisone (10 mg daily), mesalazine (1 g daily) and metronidazole (500 mg daily), and infliximab was added to the regimen. Six weeks after starting with the infliximab, he presented with skin lesions on his right thumb and forearm. He did not recall preceding trauma. He reported caring for fishes in a domestic aquarium. On physical examination, the thumb was erythematous and scaly, and there were two red and painful inflammatory papules on the distal forearm and multiple scattered subcutaneous nodules on the ipsilateral proximal forearm and distal arm with a sporotrichoid pattern (Fig. 1a). Regional lymphadenopathy was absent and a general examination was otherwise unremarkable. A biopsy was done. Microscopic examination of the skin biopsies revealed necrotizing and granulomatous inflammation. A Ziehl-Neelsen stain revealed many acid-fast bacilli, and a photochromogenic mycobacterium was grown in culture within 10 days. It was identified as Mycobacterium marinum by 16S rRNA gene sequencing methods.Therapy with ethambutol, 1200 mg per day, and rifampicin, 600 mg per day, was started and infliximab was discontinued.One month later, the skin lesion on the thumb had improved but the subcutaneous nodules on the forearm had increased markedly in size and new ulcerated lesions had appeared on the forearm. In addition, a sinus with purulent discharge had developed at the site of the distal lesion (Fig. 1b) from which M. marinum was cultured. At that time, clarithromycin, 500 mg twice daily, was added. Two months later, the size of the previous ulcerated nodules had decreased, but new red and ulcerated lesions had appeared on the previous nodules. No organisms were found by Ziehl-Neelsen staining of the pus from the new lesions, and culture on Löwenstein-Jensen medium did not grow organisms. Due to worsening of rectal symptoms, immunosuppressive therapy with 6-mercaptopurine (150 mg daily) was started. At mo...

Seroprevalence of T. cruzi infection in Latin American pregnant women coming from Bolivia and Paraguay is high. Those women should be screened for T. cruzi to control mother-to-child transmission in non-endemic areas.

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