Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs–new uses” repurposing strategy to open a new CSC-targeted chemoprevention era.     

Unusual presentation of herpes simplex virus infection in a boxer: ‘Boxing glove herpes’

Herein, we describe a patient with lesions of cutaneous herpes simplex virus 1 (HSV‐1) infection over the knuckles of both hands in the context of an outbreak among boxers. Interestingly, the infection had an unusually long duration (4 weeks), and was not acquired directly through skin‐to‐skin contact, as it usually does among athletes (herpes gladiatorum). In our case, transmission was acquired through the use of shared boxing gloves contaminated by HSV‐1. To the best of our knowledge, herpes gladiatorum, or wrestler's herpes, has not been described previously in boxers and infection over the knuckles is not commonly reported.     

Diagnostic criteria in proliferative verrucous leukoplakia: Evaluation

Objectives: to evaluate the ability of the diagnostic criteria proposed by Cerero et al in 2010 to perform an early diagnose in patients with proliferative verrucous leukoplakia. Study Design: retrospective study with patients diagnosed with leukoplakia at Oral Medicine Service at Oral Medicine and Surgery Department at Dentistry Faculty at Universidad Complutense of Madrid. Results: the criteria were applied in 116 patients, turning positive in 40 cases. Out of these, 24 (60%) had been previously diagnosed with PVL. Most frequent criteria were major criteria A and E, concerning lesion’s site and histopathology, and minor criteria b and c, concerning sex and smoking habit. Conclusions: diagnostic criteria developed by Cerero et al can be a useful tool for an early diagnose of PVL, as in 60% of the cases, the criteria would have allowed to make an early diagnose of the disease. Key words:Proliferative verrucous leukoplakia, criteria, diagnose, early.     

A pilot clinical study of hair grafting in chronic leg ulcers

Epidermal sheets spread centrifugally postinjury from the hair follicle infundibulum to reepithelialize the wound bed. Healing progresses faster in skin areas rich in terminal hair follicles. These observations are consistent with the role of the hair follicle as a major reservoir for progenitor cells. To evaluate the feasibility and potential healing capacity of autologous scalp follicular grafts transplanted into the wound bed of chronic leg ulcers, 10 patients with ulcers of an average 36.8 cm² size and a 10.5‐year duration were included in this pilot study. Within each ulcer we randomly assigned a 2 × 2 cm “experimental” square to receive 20 hair grafts and a nongrafted “control” square of equal size. The procedure seemed to be safe, although major unrelated complications occurred in two patients. At the 18‐week end point, we observed a 27.1% ulcer area reduction in the experimental square as compared with 6.5% in the control square (p = 0.046) with a maximum 33.5% vs. 9.7% reduction at week 4 (p = 0.007). Histological analyses showed enhanced epithelialization, neovascularization, and dermal reorganization. We conclude that terminal hair follicle grafting into wound beds is feasible in an outpatient setting and represents a promising therapeutic alternative for nonhealing chronic leg ulcers.     

HLA class II alleles in patients with multiple sclerosis in the Biscay province (Basque Country,Spain)

Genetic susceptibility to multiple sclerosis (MS) is associated with genes of the major histocompatibility complex, particularly with the HLA DRB1*1501-DQA1*0102-DQB1*0602 haplotype in Caucasians. To investigate the association of DRB1, DQA1 and DQB1 alleles and haplotypes with MS in Biscay, Basque Country, northern Spain, we examined 197 patients and 200 regionally matched controls. High resolution HLA class II typing was performed by polymerase chain reaction followed by sequence-specific oligonucleotide probe hybridization. Several alleles were overrepresented in MS patients compared with those of controls: DRB1*0402, DRB1*1303, DRB1*1501, DQA1*0102, DQB1*0301, and DQB1*0602. DQB1*0602 was the only potentially predisposing allele for MS that withstood Bonferroni correction and maintained the association in a logistic regression model. On the other hand, several alleles showed lower frequencies in the MS group: DRB1*0101, DQA1*0101, DQB1*0303, and DQB1*0501, but only DRB1*0101 and DQB1*0303 maintained a negative association with the disease in the regression analysis. Three haplotypes were identified as potentially predisposing for MS in our population: DRB1*1501-DQA1*0102-DQB1*0602, DRB1*0402-DQA1*0301-DQB1*0302, and HLA-DRB1*013-DQA1*05-DQB1*0301. Additionally, three haplotypes associated with a lower risk for MS were identified, exhibiting DRB1*0101-DQA1*0101-DQB1*0501 the strongest negative association with MS [12% in controls vs. 3.8% in MS, P _c = 0.00047, OR = 0.290 (95% CI = 0.160–0.528)], and suggesting, therefore, a putative protective role for this haplotype in the population under study.