Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention

Cardiovascular imaging 2011 in the International Journal of Cardiovascular Imaging

Cardiovascular Aspects of Radiolog

Risk factors associated with recurrent carotid artery stenosis

The aim of this open, perspective study was to determine the impact of risk factors, excluding the type of closure of the arteriotomy, in the development of recurrent carotid stenosis following carotid endarterectomy. One hundred and ninety-eight patients, who underwent a total of 221 carotid endarterectomies, were evaluated postoperatively with duplex scanning 1 month after the operation and every 6 months thereafter for a period of 6-120 months (mean duration of follow-up: 44 months). There were 149 (75.3%) men and 49 (24.7%) women with a mean age of 66.8 years (age range 38-92 years). Diabetes mellitus was present in 62 patients (31.3%), hypertension in 134 (67.7%), coronary artery disease in 130 (65.7%), hypercholesterolemia in 70 (35.4%), and smoking habit in 166 (83.8%). Indications for carotid endarterectomy were asymptomatic carotid stenosis > 70% in 20 (10.1%) patients and symptomatic stenosis > 50% in 178 (89.9%), 129 (65.2%) of whom had a history of transient ischemic attacks and 49 (24.7%) of previous stroke. General anesthesia was used in 197 (89.1%) operations and local anesthesia in 24 (10.9%). Deep endarterectomy with primary closure of the arteriotomy using 5/0 running suture was performed in this group of patients. One patient: (0.5%) died during the perioperative period. Five (2.5%) patients had a transient ischemic attack and three (1.5%) a nonfatal stroke in the immediate postoperative period, six (3.0%) a persistent cranial nerve injury, and two a hematoma, and three patients had delayed postoperative recovery. Twenty-six (13.1%) patients were transferred to the Intensive Care Unit postoperatively, Recurrent carotid stenosis > 50% was identified in eight patients (4.0%) and it was asymptomatic in all cases; Mean interval between endarterectomy and development of restenosis was 47.4 months (range 6-118 months). Factors such as clinical presentation, age, sex, diabetes mellitus, hypertension, coronary artery disease, hypercholesterolemia, and smoking habit were not found to be significantly associated with the development: of restenosis (Chi-square). Smoking, coronary artery disease, and normal choresterol levels were connected with a statistically nonsignificant tendency toward higher rates of restenosis. Recurrent carotid stenosis following carotid endarterectomy was not significantly associated with any of the risk factors studied in this series

Middle aortic syndrome - A case report

A 47-year-old woman presented with a 2-year history of severe proximal claudication symptoms in both legs. Digital subtraction aortography (DSA) showed a localized occlusion of the infrarenal abdominal aorta. A longitudinal arteriotomy and an endarterectomy of the aorta were performed. The arteriotomy was closed with a polytetrafluoroethylene (PTFE) patch. Postoperatively, the follow-up demonstrated a normal aorta with all pedal pulses palpable. In patients with the above symptoms, middle aortic syndrome should be included in the differential diagnosis