Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-“decoy” strategy

MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET(K842E) retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET(K842E) used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience.

Innovative Online Curriculum Writing: A Practical Approach for Multiple Authors/Multiple Locations

The technology-based writing method described here enabled collaboration from distant locations. A comprehensive and well-integrated 4-H quilt curriculum was the goal. Seven writers used an electronic activity template based on 4-H Cooperative Curriculum System standards. A hyper-linked spreadsheet was developed. Each writer input their writing from the template to their separate sheet, which was hyper-linked to the master spreadsheet. Using FTP client software, all writers had access to updated materials on the master spreadsheet at all times. The writer/editor could see all work, monitor duplicate efforts, and put writing into one voice. A 284-page coherent and comprehensive curriculum resulted

Laser thermal ablation to treat a recurrent soft-tissue sarcoma of the leg : A case report

We present the case of a 52-year-old male patient with recurrence of a soft-tissue sarcoma of the left leg treated with percutaneous laser ablation. The patient received the diagnosis of sarcoma for the first time in 2011; further local recurrences and a pulmonary metastatic spread occurred during follow-up, so the patient has been treated several times with chemotherapy, limb-sparing surgery and radiotherapy. In September 2017, a new local recurrence of sarcoma occurred, for which limb amputation was proposed but refused by the patient. Laser ablation with ultrasound guidance was performed, with complete ablation at 6 months and limb salvage

Biomassa seca e relação raiz-parte aérea de acessos de paspalum submetidos ao alagamento do solo.

In general, tropical pastures have limitations of use under conditions of stress by flooding. The purpose was to measure the flooding stress response in dry biomass and root/shoot ratio of five accessions of Paspalum (Paspalum regnellii, BRA 23469, BRA 23540, BRA 23671 and 21377 BRA) and Brachiaria brizantha cv. Marandu at the end of the stress period and after recovery under ideal water conditions. The greater shoot biomass was observed in Brachiaria brizantha, being similar among Paspalum accessions. The root biomass and the root/shoot were negatively affected by flooding and also by the collection period at the end of 28 days of stress. Flooding considerably influenced biomass allocation to roots and root/shoot ratio Paspalum genotypes. The allocation model is important for understanding the strategies adopted by these plants to acquire competitive advantages under water stress

Trends and risk factors for syphilis infection in Piedmont Region, Italy, 2002-2008

Background: This work aims to analyze trends of syphilis infections in the Piedmont Region (Italy) between 2002 and 2008, and to evaluate risk factors for infection. Methods: Syphilis trends were described according to socio-demographic characteristics, sexual behavior, condom use, number of partners and HIV infection. Independent risk factors for syphilis among men having sex with men (MSM), men having sex with women (MSW), and women were identified through logistic regression comparing cases with 12,773 negative patients. Results: Between 2002 and 2008, 1,046 cases of syphilis were diagnosed, with peaks in 2004 and 2007. The risk of a syphilis diagnosis was independently associated with being older than 24, having a low education level, homosexual behavior, HIV self-reported infection (for MSM and MSW), number of partners (for MSW and women) and non- consistent condom use (for women). Conclusions: Recent outbreaks suggest that the attention to syphilis can’t be lowered. Screening, treatment of cases and notification of partners should be reinforced and integrated with sexual health education and counselling in high-risk environments. Surveillance data must be continuously collected