[Vemurafenib (Zelboraf) in the Therapy of Melanoma].

[Vemurafenib (Zelboraf) in the therapy of melanoma].

Magy Onkol. 2013 Jun; 57(2): 110-3
Liszkay G

The incidence of malignant melanoma is continuously rising, but the therapy of advanced melanoma remains insufficient. Advances in the understanding of the immunological and genetical background resulted in the development of a new target therapeutic agent, vemurafenib (Zelboraf) accepted by the FDA in 2011 and by the EMA in 2012. Vemurafenib improved the overall and progression-free survival of untreated melanoma with the mutation BRAF V600E. In a phase III study vemurafenib was associated with a 63% reduction in the risk of deaths compared with dacarbazine and of 74% in the risk of either death or disease progression. Objective response was 48% in the vemurafenib and 5% in the dacarbazine arm. Vemurafenib has special side effects, surprisingly even secondary skin tumors. Additional research is needed to understand the mechanism of drug resistance and to find new targeted therapeutic agents and combinations. HubMed – drug


Design and Application of Magnetic-based Theranostic Nanoparticle Systems.

Recent Pat Biomed Eng. 2013 Apr 1; 6(1): 47-57
Wadajkar AS, Menon JU, Kadapure T, Tran RT, Yang J, Nguyen KT

Recently, magnetic-based theranostic nanoparticle (MBTN) systems have been studied, researched, and applied extensively to detect and treat various diseases including cancer. Theranostic nanoparticles are advantageous in that the diagnosis and treatment of a disease can be performed in a single setting using combinational strategies of targeting, imaging, and/or therapy. Of these theranostic strategies, magnetic-based systems containing magnetic nanoparticles (MNPs) have gained popularity because of their unique ability to be used in magnetic resonance imaging, magnetic targeting, hyperthermia, and controlled drug release. To increase their effectiveness, MNPs have been decorated with a wide variety of materials to improve their biocompatibility, carry therapeutic payloads, encapsulate/bind imaging agents, and provide functional groups for conjugation of biomolecules that provide receptor-mediated targeting of the disease. This review summarizes recent patents involving various polymer coatings, imaging agents, therapeutic agents, targeting mechanisms, and applications along with the major requirements and challenges faced in using MBTN for disease management. HubMed – drug



Drug Deliv Transl Res. 2013 Jun 1; 3(3): 260-271
Sadekar S, Linares O, Noh G, Hubbard D, Ray A, Janát-Amsbury M, Peterson CM, Facelli J, Ghandehari H

The purpose of this study was to model data from a head to head comparison of the in vivo fate of hyper-branched PAMAM dendrimers with linear HPMA copolymers in order to understand the influence of molecular weight (MW), hydrodynamic size (Rh) and polymer architecture on biodistribution in tumor-bearing mice using compartmental pharmacokinetic analysis. Plasma concentration data was modeled by two-compartment analysis using Winnonlin® to obtain elimination clearance (E.CL) and plasma exposure (AUCplasma). Renal clearance (CLR) was calculated from urine data collected over 1 week. A plasma-tumor link model was fitted to experimental plasma and tumor data by varying the tumor extravasation (K4, K6) and elimination (K5) rate constants using multivariable constrained optimization solver in Matlab®. Tumor exposures (AUCtumor) were computed from area under the tumor concentration time profile curve by the linear trapezoidal method. Along with MW and Rh, polymer architecture was critical in affecting the blood and tumor pharmacokinetics of the PAMAM-OH dendrimers and HPMA copolymers. Elimination clearance decreased more rapidly with increase in hydrodynamic size for PAMAM-OH dendrimers as compared to HPMA copolymers. HPMA copolymers were eliminated renally to a higher extent than PAMAM-OH dendrimers. These results are suggestive of a difference in extravasation of polymers of varying architecture through the glomerular basement membrane. While the linear HPMA copolymers can potentially reptate through a pore smaller in size than their hydrodynamic radii in a random coil conformation, PAMAM dendrimers have to deform in order to permeate across the pores. With increase in molecular weight or generation, the deforming capacity of PAMAM-OH dendrimers is known to decrease, making it harder for higher generation PAMAM-OH dendrimers to sieve through the glomerulus as compared to HPMA copolymers of comparable molecular weights. PAMAM-OH dendrimer had greater tumor extravsation rate constants and higher tumor to plasma exposure ratios than HPMA copolymers of comparable molecular weights which indicated that in the size range studied, when in circulation, PAMAM-OH dendrimers had a higher affinity to accumulate in the tumor than the HPMA copolymers. HubMed – drug


A Review of Femtosecond Laser Assisted Cataract Surgery for Hawai’i.

Hawaii J Med Public Health. 2013 May; 72(5): 152-5
Chen M

Hawai’i has had the first US Food and Drug Administration approved femtosecond laser (LenSx as shown in figure) for cataract surgery since early 2012, a brand new laser technology for modern cataract surgery in Hawai’i. This article intends to evaluate the cost, safety, efficacy, advantages, and limitations of femtosecond laser-assisted cataract surgery through a review of the literature for the public of Hawai’i. A search was conducted using keywords to screen and select articles from PubMed. In addition, recent published peer reviewed articles pertinent to the femtosecond laser-assisted cataract surgery were selected and reviewed. Safety and efficacy of femtosecond laser-assisted cataract surgery were demonstrated in the literature, with improvements in anterior capsulotomy, phacofragmentation, and corneal incision. However, there were limitations within these studies which included small sample size and short-term follow-up. In addition, cost-benefit analysis has not yet been addressed. Long-term studies to compare the complication rate and visual outcome between the laser and conventional cataract surgery are warranted. HubMed – drug


Favorable outcomes for native hawaiians and other pacific islanders with severe traumatic brain injury.

Hawaii J Med Public Health. 2013 Apr; 72(4): 129-35
Nakagawa K, Hoshide RR, Asai SM, Johnson KG, Beniga JG, Albano MC, Del Castillo JL, Donovan DJ, Chang CW, Koenig MA

Traumatic brain injury (TBI) disproportionately impacts minority racial groups. However, limited information exists on TBI outcomes among Native Hawaiians and other Pacific Islanders (NHPI). All patients with severe TBI (Glasgow Coma Scale (GCS) <9) who were hospitalized at the state-designated trauma center in Hawai'i from March 2006 to February 2011 were studied. The primary outcome measure was discharge Glasgow Outcome Scale ([GOS]: 1, death; 2, vegetative state; 3, severe disability; 4, moderate disability; 5, good recovery), which was dichotomized to unfavorable (GOS 1-2) and favorable (GOS 3-5). Logistic regression analyses were performed to assess factors predictive of discharge functional outcome. A total of 181 patients with severe TBI (NHPI 27%, Asians 25%, Whites 30%, and others 17%) were studied. NHPI had a higher prevalence of assault-related TBI (25% vs 6.5%, P = .046), higher prevalence of chronic drug abuse (20% vs 4%, P = .02) and chronic alcohol abuse (22% vs 2%, P = .003), and longer intensive care unit length of stay (15±10 days vs 11±9 days, P < .05) compared to Asians. NHPI had lower prevalence of unfavorable functional outcomes compared to Asians (33% vs 61%, P = .006) and Whites (33% vs 56%, P = .02). Logistic regression analyses showed that Asian race (OR, 6.41; 95% CI, 1.68-24.50) and White race (OR, 4.32; 95% CI, 1.27-14.62) are independently associated with unfavorable outcome compared to NHPI. Contrary to the hypothesis, NHPI with severe TBI have better discharge functional outcomes compared to other major racial groups. HubMed – drug