Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/ Documents/Bookmarked%20Practice%20Guidelines/ HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations.

/pdf/aasld-practice-guideline-management-of-hepatocellular-51bocalv0r.pdf

AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update

Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.

Understanding biophysicochemical interactions at the nano–bio interface

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.20933

Management of hepatocellular carcinoma.

Pathology and genetics of tumors of soft tissue and bone

Nanoparticles — particles in the size range 1–100 nm — are emerging as a class of therapeutics for cancer. Early clinical results suggest that nanoparticle therapeutics can
show enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumours and active cellular uptake. Here, we
highlight the features of nanoparticle therapeutics that distinguish them from previous anticancer therapies, and describe how these features provide the potential for
therapeutic effects that are not achievable with other modalities. While large numbers of preclinical studies have been published, the emphasis here is placed on preclinical and clinical studies that are likely to affect clinical investigations and their implications for advancing the treatment of patients with cancer.

Nanoparticle therapeutics: an emerging treatment modality for cancer

Doxorubicin (Adriamycin) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity. Cardiotoxicity was monitored by noninvasive methods, and endomyocardial biopsy specimens were studied by electronmicroscopy. Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by standard intravenous injection. Both groups were studied prospectively and were well matched by risk factors for doxorubicin cardiotoxicity. The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area (range, 360 to 1500 mg/m2) compared with 465 mg/m2 (range 290 to 680 mg/m2) in the control group (p = 0.002). Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens, precluding further doxorubicin administration, as compared with two of 21 patients receiving the drug by continuous infusion (p less than 0.02). The mean pathologic score for the infusion group, 0.9, was lower than the mean for the control group, 1.6 (p = 0.004). Antitumor activity was not compromised. Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity.

Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion.

A prosthetic valve comprises a poppet, a seat and a restraining element. The poppet, seat and restraining element include an insertion form for percutaneously inserting into a fluid passageway within a living body and an operational form for operating within the fluid passageway. The valve is self-expanding so that upon insertion the valve automatically assumes the operational form. In the operational form the poppet is movably restrained between the valve seat and restraining element. The poppet seals against the valve seat to prevent fluid flow through the valve and unseats from the valve seat to permit fluid flow through the valve.

Prosthetic valve for percutaneous insertion

Two mechanical devices for the purpose of occluding vessels are presented.Cotton tails, small metallic segments with attached cotton threads, will effectively occlude small arteries of approximately 2 mm. in diameter.Wool coils, 5 cm. segments of the outer portion of steel guidewires with attached wool strands, obstructed major vessels just beyond the tip of the catheter.The use of these devices has been investigated in dogs and then applied clinically in the occlusion of renal arteries in patients with hypernephroma.

Mechanical devices for arterial occlusion.

Despite an intensive search, few water-soluble paclitaxel derivatives have been shown to have a therapeutic index superior to paclitaxel itself. We now report a water-soluble poly(l-glutamic acid)-paclitaxel conjugate (PG-TXL) that produces striking antitumor effects with diminished toxicity. A single i.v. injection of PG-TXL at its maximum tolerated dose (defined as that dose that produces a maximum 12–15% body weight loss within 2 weeks after a single i.v. injection) equivalent to 60 mg of paclitaxel/kg and at even a lower dose equivalent to 40 mg of paclitaxel/kg resulted in the disappearance of an established implanted 13762F mammary adenocarcinoma (mean size, 2000 mm 3 ) in rats. (An equivalent dose of PG-TXL is the amount of conjugate that contains the stated amount of paclitaxel.) Similarly, mice bearing syngeneic OCA-1 ovarian carcinoma (mean size, 500 mm 3 ) were tumor-free within 2 weeks after a single i.v. injection of the conjugate at a dose equivalent to 160 mg of paclitaxel/kg. The conjugate has little if any intrinsic tubulin polymerization activity in vitro and is > 20 times less potent in supporting the growth of a paclitaxel-dependent CHO mutant cell line. PG-TXL has a prolonged half-life in plasma and greater uptake in tumor as compared with paclitaxel. Furthermore, only a small amount of total radioactivity from PG-[ 3 H]TXL was recovered as free [ 3 H]paclitaxel in either the plasma or the tumor tissue within 144 h after drug injection. Histological studies of tumor tissues obtained from mice treated with PG-TXL show fewer apoptotic cells but more extensive tumor necrosis as compared with paclitaxel treatment. These data suggest that in addition to its role as a carrier for selective delivery of paclitaxel to the tumor, PG-TXL exerts distinct pharmacological actions of its own that may contribute to its remarkable antitumor efficacy.

https://cancerres.aacrjournals.org/content/canres/58/11/2404.full.pdf

Complete Regression of Well-established Tumors Using a Novel Water-soluble Poly(l-Glutamic Acid)-Paclitaxel Conjugate

https://www.chem.tamu.edu/rgroup/wooley/chem689/Articles/CHEM%20689-Supp/CHEM%20689-Supp/Polymeric%20conjugates.pdf

Sidney Wallace

Papers

Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion.

Prosthetic valve for percutaneous insertion

Mechanical devices for arterial occlusion.

Complete Regression of Well-established Tumors Using a Novel Water-soluble Poly(l-Glutamic Acid)-Paclitaxel Conjugate

Polymer-Drug Conjugates: Recent Development in Clinical Oncology