Diagnosis of Allergic Dermatoses in Skin of Color.

PURPOSE OF REVIEW: This review aims to deliver a comprehensive report of the most recent knowledge on diagnosing allergic dermatoses in skin of color (SOC) patients. RECENT FINDINGS: Allergic dermatoses can affect populations of all backgrounds. However, racial/ethnic variations in epidemiology, clinical features, and associated allergens have been reported. Nuances in the approach to diagnosis, including the assessment of erythema and interpretation of patch tests, are important considerations when treating patients with SOC. In this review, we outline various manifestations of allergic dermatoses in SOC with a focus on important clinical presentations and diagnostic tools, aiming to support clinicians in accurate recognition of diseases, thereby opening avenues to improve outcomes across diverse skin types.

Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer: Evaluation of a biological-systems approach to cancer therapy (U.S. FDA IND-BB 10091; NCT 02046174, NCT 01053013).

OBJECTIVE: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here. METHODS: Forty-eight mCRC patients (30 females; 18 males), who had failed all available, approved treatments, underwent RMB implantation (8 RMB/kg body weight) up to 4 times in phase I and phase IIa open-label trials. Physicals, labs [tumor and inflammation markers, lactate dehydrogenase (LDH)] and positron emission tomography-computed tomography (PET-CT) imaging to measure number/volume and metabolic activity of the tumors were performed pre- and 3-month-post-implantation to evaluate safety and initial efficacy (as defined by biological responses). PET-CT maximum standard uptake value (SUVmax) (baseline and d 90; SUVmax ≥2.5), LDH, and carcinoembryonic antigen (CEA) and/or cancer antigen 19-9 (CA 19-9) response (baseline, d 30 and/or d 60) were assessed and compared to OS. RESULTS: Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in 75% of patients. Fluorodeoxyglucose (FDG)-positive lesions (phase I, 39; 2a, 82) were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV (10) plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders (R) (d 0-60, 290.4-333.9), but increased steadily in Non-responders (NR) (d 0-60, 382.8-1,278.5) (d 60, P=0.050). Responders to RMBs, indicated by the changes in the above markers, correlated with OS (R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006). CONCLUSIONS: The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to mCRC. A phase III clinical trial is planned.

First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors.

PURPOSE: Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective. METHODS: Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075). Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. RESULTS: RMBs were well tolerated at both dose levels (mean 660.9 per implant). AEs were (Grade 1/2) with no treatment-related SAEs. CONCLUSION: The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.