Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy.

Objective To evaluate the therapeutic efficacy of a novel modular polymer platform in the treatment of HNSCC. Study Design in vivo study. Setting Academic research laboratory. Subjects and Methods C3H/HeJ mice and SCID Beige mice were randomized to receive implantation of (1) no polymer; (2) plain polymer; (3) plain polymer with local cisplatin injection; (4) cisplatin polymer. The two groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days; (2) no radiation. Tumor size was measured until the mice were euthanized. At necropsy, the tumors were excised and weighed. Results Our results using this novel polymer platform demonstrate a significant reduction in tumor growth. The cisplatin secreting polymer effectively reduced human head and neck tumor growth in SCID mice by 17 fold (P < 0.01); and SCCVII/SF tumors in the C3H/HeJ mice by over 16-fold (P < 0.01) as compared to control, plain polymer, and plain polymer + intratumoral cisplatin injection groups. We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to the radiation alone group and the control group. Conclusion Herein we demonstrate the efficacy of a novel polymer platform in delivering cisplatin to a partially resected SCC in a murine model. Our results indicate that this polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC.

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Ectopic parathyroid adenomas are found in up to 16% of initial operations 1 and 50% of reoperations 2 for primary hyperparathyroidism. A small fraction of ectopic glands are located well outside the bounds of a conventional low cervical Kocher-type exposure. Examples include mediastinal adenomas, which are generally inferior glands embryologically, and undescended superior adenomas. Undescended superior parathyroid glands are found in fewer than 0.1% of cases and are defined as glands that are located 1 cm or more cephalic to the upper pole of the thyroid gland.3 They may be found along or within the pharyngeal wall and almost never lie above the carotid bifurcation. Intraneural parathyroid adenomas are distinctively rare. We report the second published case (to our knowledge) of an ectopic parathyroid adenoma arising within the hypoglossal nerve. REPORT OF A CASEA 40-year-old man with persistent hyperparathyroidism status post 2 failed parathyroidectomies was evaluated for a third parathyroidectomy. He had a 2-year history of hyperparathyroidism (calcium, 15.0 mg/dL [to convert to millimoles per liter, multiply by 0.25]; parathyroid hormone, 265 pg/mL [to convert to nanograms per liter, multiply by 1]) complicated by nephrolithiasis, pathologic fractures, and evolving renal failure. His disease was refractory to medical management with hydration, furosemide, pamidronate, and maximal doses of cinacalcet. The results of initial localization with sestamibi imaging and ultrasonography were negative, prompting a selective venous sampling study, which localized to the high right internal jugular region between C2 and C4. This finding prompted magnetic resonance imaging (Figure 1) as well as another sestamibi/ single-photon emission computed tomographic imaging study with increased acquisition times and magnified views of the nonstandard region of interest. Based on this information, a third operation was planned, targeting a 9.8-mm lesion medial to the mandibular ramus and adjacent to the internal carotid artery.A fusiform enlargement of the proximal portion of the hypoglossal nerve was identified adjacent to the right cervical internal carotid artery, near the skull base (Figure 2). It was initially thought to be a schwannoma. The findings of a biopsy of the mass confirmed the presence of hypercellular parathyroid tissue. To remove the adenoma, the nerve sheath was incised longitudinally. Sharp dissection was performed with sparing of most of the nerve. Intraoperative parathyroid hormone levels decreased promptly from a baseline of 375 pg/mL to 26 pg/mL 10 minutes after excision.The patient's calcium levels normalized by the following day. Transient tongue deviation to the right was noted initially but resolved after 2 months, at which time the tongue was observed to move normally.

The effects of progesterone and estradiol on cholesteryl ester (CE) formation by monocyte-derived human macrophages were examined. Formation was assessed from incorporation of 14C-cholesterol during a 20-h incubation with hormone and from that of 3H-oleate (3 h) after hormone removal. Progesterone inhibited cholesterol into CE and decreased CE cellular levels. Inhibition: 1) was reversed by progesterone removal; 2) was independent of the progesterone receptor (not blocked by the receptor antagonist RU40555); and 3) exhibited specific structural requirements; 11alpha-OH-progesterone was inhibitory, whereas its stereoisomer 11beta-OH-progesterone was not. In contrast to progesterone, estradiol was ineffective. We had reported that dexamethasone enhanced CE accumulation by human macrophages (1). In this study, we describe similar effects of the endogenous steroid, cortisol, and of the most widely prescribed glucocorticoid, prednisolone. Both steroids increased CE formation from two folds, in the presence of cholesterol-liposomes, to five folds, in the presence of modified low-density lipoprotein. Progesterone (0.1-1 micromol/L), added during glucocorticoid treatment, blocked this increase. The progesterone block: 1) was duplicated by the steroid receptor inhibitor RU40555; 2) was not reversed by hormone removal; and 3) reflected inhibition of glucocorticoid-induced increases in messenger RNA for acyl-CoA-cholesterol:acyl transferase. Thus, progesterone exerted two effects on macrophages: it acutely inhibited CE formation, and it prevented glucocorticoid-induced increases in acyl-CoA-cholesterol-acyl transferase gene expression and CE synthesis.