The VHI-10 is a powerful representation of the VHI that takes less time for the patient to complete without loss of validity. Thus, the VHI-10 can replace the VHI as an instrument to quantify patients' perception of their voice handicap.

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The persistence of genetic damage produced by alkylating agents 1 as well as the antagonism of essential biochemical processes such as transcription can have lethal consequences for malignant cells. 2 Both mechanisms have been identified in studies to uncover the reasons for the efficacy of cisplatin in the treatment of several cancers. 2a, 3 We describe a synthetic strategy to create bifunctional molecules that produce DNA adducts capable of binding the estrogen receptor (ER), which is aberrantly expressed in many breast cancer cells. 4 It is speculated that DNA adducts that form complexes with the ER will be poorly repaired in these cells because they are camouflaged from detection by DNA repair enzymes. Consequently, the DNA lesions persist. Furthermore, the DNA adducts would be expected to act as "molecular decoys" capable of displacing the ER from its natural targets and antagonizing its role in malignant growth. In healthy cells, where the abundance of the ER is minimal, no such ER-DNA adduct complexes will be present, and the cell should survive. 5 In this report we describe the design and synthesis of compound 1, a bifunctional agent that can form covalent DNA adducts capable of binding the ER with high affinity and specificity. We show that 1 has selective toxicity toward ER+ breast cancer cells compared to ER-cells in vitro.Compound 1 consists of a bis-chloroethyl aniline mustard as the DNA alkylating unit tethered to estradiol, the natural ligand for the ER. The site of substitution of estradiol in 1 was based on reports that relatively large alkyl groups can be attached at the 7α position with retention of high affinity for the ER 6 . The synthetic strategy for 1 is shown in Scheme 1. Compound 7, a key compound in the synthesis, was prepared by a modification of a published strategy. 7 Briefly, 3 was functionalized with a 6-carbon chain at the 7-position in α-stereochemistry to provide the alkenyl steroid 4. Efficient reduction of the 6-oxo group in 4 was achieved with Et 3 SiH/BF 3 .Et 2 O; however, this treatment also caused the loss of 3,17-tetrahydropyranoxy (THP) groups producing diol 5. The 3,17-OHs of 5 were reprotected with THP groups to afford 6, followed by oxidation of the alkene at the terminus of the linker to provide alcohol 7. Steroid alcohol 7 was converted to bromide 8, which was subsequently allowed to react with a protected ethanolamine to give 9. Compound 9 was desilylated with tetrabutylammonium fluoride (TBAF) and converted to a carbonate Next, the ability of 1 to modify DNA covalently was investigated. Plasmid DNA was incubated with 100 μM [ 14 C]-1 10 at 37 °C for up to 6 h. After unbound 1 was removed by phenol-CHCl 3 extraction and ethanol precipitation, the radioactivity associated with DNA was measured. The amount of radioactivity bound to DNA increased at a constant rate over the 6-h period indicating the formation of covalently bound 1 (see Supporting Information). Based on previous studies on DNA alkylation by nitrogen mustards, 11 it is likely that covalent adducts of...

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The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice, and hearing. The present manuscript describes a study that was conducted in which a biologic scaffold derived from porcine (pig) extracellular matrix (ECM) was used to repair the defect following a hemilaryngectomy procedure in dogs. The ECM-augmented repair was compared with a control standard strap muscle (STM) procedure. The animals were sacrificed after 24 weeks at which time anatomic and histologic analyses were conducted. The ECM repair resulted in a macroscopic and microscopic reconstruction of laryngeal tissue that was superior to that observed with the STM procedure. The importance of regenerated tissue having the same structural and functional characteristics of native tissue is emphasized. A discussion of the mechanisms of ECM remodeling is presented along with the implications of such remodeling in the repair of laryngeal structures.