Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose.Experimental Design: Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m 2 on day 1 and gemcitabine at 1,250 mg/m 2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m 2 . Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity <25%. Quality of life was assessed using EORTC-QLQ-C30.Results: Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m 2 . Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3-50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores.Conclusions: Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine.

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Vitiligo vulgaris is a common disease throughout the world although its pathogenesis is not yet known. The most frequent treatment used for vitiligo is PUVA (psoralen plus ultraviolet A) and topical steroids but against stable refractory vitiligo, various other surgical techniques have been developed such as autografting, epidermal grafting with suction blisters, epithelial sheet grafting, and transplantation of cultured melanocytes. We have discovered a new method using ultrasonic abrasion, seed-grafting and PUVA therapy. The ultrasonic surgical aspirator abrades only the epidermis of recipient sites. This easily and safely removes only the epidermis, even on spotty lesions or intricate regions which are difficult to remove using a conventional motor-driven grinder or liquid nitrogen. Epidermal seed-grafting can cover more area than sheet-grafting, and subsequent PUVA treatment can enlarge the area of pigmentation with coalescence of adjacent grafts. In this article, we provide a general overview of the current surgical therapies including our method for treating stable refractory vitiligo.

CD44 is a principal cell-surface receptor for hyaluronate and is found on a wide variety of cells. CD44 plays an important role in lymphocyte homing, lymphohemopoiesis, and T-cell activation as well as in cell motility and migration. CD44 is expressed on the cell surface of epidermal Langerhans cells (LC), and is one of the candidates for molecules that are involved in the migratory capability of LC, but little is known about its regulatory properties. We examined the modulatory effects of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 on the CD44 expression in LC. We found 1) that TNF-alpha significantly up-regulated the expression of CD44 in a concentration-dependent manner, 2) that IL-10 down-regulated the expression of CD44 in a concentration-dependent manner, 3) that the effect of TNF-alpha or IL-10 was readily detectable as early as 24 h after the initiation of culture, and 4) that the simultaneous addition of TNF-alpha and IL-10 mutually neutralized the effect of each other. These data suggest that in the epidermal microenvironment the expression of CD44 in LC may be reciprocally regulated by TNF-alpha and IL-10, both of which are known to be produced by surrounding keratinocytes.