134 research outputs found
Synthesis of monensin derivatives and their effect on the activity of ricin A-chain Immunotoxins
No full text
Antibody-targeted leucinostatin A.
No full textThis paper describes chemical modification of the toxic agent Leucinostatin A and its conjugation with a monoclonal antibody. The molecule, isolated from a culture filtrate of Paecilomyces marquandii (Massee) Hughes, is a nonapeptide antibiotic with cytotoxic and phytotoxic properties. To evaluate its toxicity, and to improve its specificity as an antitumor agent, the molecule was conjugated to the monoclonal antibody AR-3, specific to human colorectal and ovarian carcinomas. The targeting ability of AR-3, bearing different amounts of toxic agent, was tested on related and unrelated cell lines. Stability of the ester linkage between Leucinostatin A and AR-3 was also studied.
In this study we show that coupling of Leucinostatin A with a tumor-directed monoclonal antibody is a practical way to increase both the cytotoxicity and selectivity of the chemotherapeutic agent
Production of PEGylated nanocapsules through solvent-displacement in confined impinging jets mixers
No full textThe growth of importance of nanocapsules (and other particulate systems) in different fields requires fast and reproducible methods for their production. Confined impinging jet mixers were successfully used for the production of nanospheres and are now tested for the first time for the production of nanocapsules. This work focuses on the understanding of formation mechanisms and on the quantification of the effect of the most important operating parameters involved in their production. Solvent displacement is employed here for the assembly of the nanocapsules by using a PEGylated derivative of cyanoacrylate as copolymer. A comparison with nanospheres obtained under the same operating conditions is also reported. Results show that the oil-to-copolymer mass ratio (MR) is the main factor affecting the final size distribution and that small nanocapsules are obtained only at low oil-to-copolymer MR. The effect of mixing is significant, proving that mixing of solvent and antisolvent also affects the final size distribution; this depends mainly on the inlet jet velocity, but the size of the mixer is also important. The Reynolds number may be useful to take this into account for geometrically similar systems. Quenching by dilution allows to stabilize the nanocapsules, evidencing the role of aggregation and ripening
The dimensional stability of a CFRP structure probed with sub-micrometer accuracy in varying external condition
No full textThe paper presents the thermal deformations of a CFRP High Dimensional Stability Structure. With an experimental facility designed and tested to undergo negligible deformations, ten points of the UV-spectrometer' support (Test Article, TA) have been monitored with triaxial capacitive transducers, both in vacuum and in dry nitrogen atmosphere, with temperature variations in the range 253÷333K. The measured deformations differ from point to point: +4.05±0.01μm/K has been the largest dimensional variation measured in one point of TA and in one direction, whereas -0.05±0.02μm/K has been the smallest one, in another point and in a different direction. All the obtained results agree within ±2μm/K with the computer simulated tests accomplished in the design of TA. A complete analysis of the sources of uncertainty assures the displacement' measurements' accuracy has been ≤0.1μm, whatever the experimental conditions. The dimensional stability of the TA has been verified finally with a series of hygro-thermal cycles The results show that permanent deformations not larger than ±2μm occurred in a limited number of points
Self-assembly drug conjugates for anticancer treatment
No full textSelf-assembly drug conjugate preparation is a promising approach to improve activity and penetration through physiological barriers of potent small molecules, as well as to reduce any side effects. Drug conjugates can self-assemble in water to form nanoparticles (NPs) that offer several advantages because: (i) they are easy to obtain; (ii) they can reach high local drug concentration in tumor tissues; and (iii) they can reduce the side effects of drugs. All these factors improve drug pharmacokinetic properties. Here, we have reviewed the scope of nanotechnology-based self-assembly drug delivery approaches focusing on prodrugs able to form NPs by self-assembly; we have also summarized the current perspective and challenges facing the successful treatment of cancer
Paclitaxel and pegylated liposomal doxorubicin in recurrent head and neck cancer: clinical and unexpected pharmacokinetic interactions
No full textBACKGROUND:
The combination of paclitaxel (PTX) with pegylated liposomal doxorubicin (PLD) is an interesting treatment for recurrent head and neck cancer. The pharmacokinetic behavior may depend on the interval between the intravenous administration of the two drugs. This study evaluates the clinical efficacy, toxicity and any possible interval-dependent pharmacokinetic interactions.
PATIENTS AND METHODS:
Thirty patients were randomized to receive 80 mg/m2 PTX weekly and 12.5 mg/m2 PLD every two weeks at administration intervals of 0, 1, 3, 12 or 24 hours. Blood sampling was performed at day 1 and 15 and pharmacokinetics of PTX, PLD and Cremophor EL were evaluated by non-compartmental analysis.
RESULTS:
Neutropenia was the most frequent side-effect (100% of patients; 30% grade 3-4). Hand-foot syndrome was severe in only 3% of patients. Overall response rate was 30%, with 3% complete responses and 27% partial responses. Stable disease and progression were 43% and 27%, respectively. Median response duration and overall median survival were 5.5 and 10 months respectively. Co-administration of PLD markedly reduced Cmax and the area under the curve (AUC), and increased PTX clearance. The differences in the PTX AUC and clearance between the 0 h and the 24 h experimental arms were statistically significant.
CONCLUSION:
The PTX/PLD combination plays a palliative role (clinical benefit in 73% of patients) and has good tolerability. The PTX pharmacokinetic profile was unexpectedly affected by different administration time intervals; in the 0 h arm the AUC was reduced to one fourth, therefore a schedule with PTX on day one, PLD on day two may be preferred
Development of functionally patent lymphatic meshes in postsurgical long-term resolution of peripheral secondary lymphedema
No full textObjective: In oncologic surgery, secondary lymphedema of male external genital organs and upper or lower limbs frequently develops as a result of excision or mechanical obstruction of collecting lymphatic trunks. We evaluated whether the short-term and long-term outcomes of microsurgical treatment of limb and genital organs improves tissue drainage in patients with secondary lymphedema by restoring the pre-existing lymphatic networks or through new lymphangiogenesis. Methods: Of 110 secondary lymphedema patients, microsurgery was performed in 45 hospitalized patients. Patients were aged 25 to 75 years, had at least third-degree lymphedema, no satisfactory results from previous physical or pharmacologic therapy, without primitive neoplasia, at least 1 year since the last postsurgical adjuvant ontological treatment, and <15 years since the previous primary oncologic lymphedema development. A microsurgical lymphovenous shunt of the spermatic cord (n = 7), a lymphovenous shunt of the lower limbs (n = 32), or lymphatic grafting of the upper limbs (n = 6) was performed. The male external genitals were treated through an innovative lymphovenous shunt of the lymphatic collectors in the pampiniform plexus of the spermatic cord. For lower limb lymphedema, the lymphatics were shunted to the collaterals or saphenous vein. For upper limb lymphedema, a shunt was performed between the lymph vessels of the jugular-supraclavicular area and those in close continuity with the axillary region. The patency of the new lymphatic pathways was assessed using Photodynamic Eye (Hamamatsu Photonic K.K., Tokyo, Japan) lymphography. Results: Six months postoperatively, 36 responding patients showed an almost complete recovery from secondary lymphedema. Lymphatic meshes, consisting of several lymphatic vessels merging into well-canalized and complex networks developing in the perianastomotic area or between the adjacent proximal anastomotic lymphatic collectors, were commonly observed in patients who positively responded to microsurgery. These complexes were never encountered in nonresponding patients or in normal, nonedematous tissue. Conclusions: Long-term postsurgical recovery from severe secondary lymphedema requires canalizing the lymphatic collectors along their original flow pattern and developing perianastomotic meshes. Because this phenomenon can be observed with the same characteristics in different tissues, such as the spermatic cord and the inguinocrural, inguinoscrotal, inguinotesticular, and brachial regions, the development of meshes seems to reflect a generalised phenomenon of local lymphangiogenesis triggered by the microsurgical procedure
- …
