Neo‐adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource‐poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

The majority of clinical trials of neo‐adjuvant therapy for breast cancer have been conducted in resource‐rich countries. We chose Nigeria, a resource‐poor country, as the major site for a phase II feasibility open‐label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo‐adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m² twice daily (2,000 mg/m² total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo‐adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.     

Psychometric Validation of the Revised Family Affluence Scale: a Latent Variable Approach

The aim was to develop and test a brief revised version of the family affluence scale. A total of 7120 students from Denmark, Greenland, Italy, Norway, Poland, Romania, Scotland and Slovakia reported on a list of 16 potential indicators of affluence. Responses were subject to item screening and test of dimensionality. Bifactor analysis revealed a strong general factor of affluence in all countries, but with additional specific factors in all countries. The specific factors mainly reflected overlapping item content. Item screening was conducted to eliminate items with low discrimination and local dependence, reducing the number of items from sixteen to six: Number of computers, number of cars, own bedroom, holidays abroad, dishwasher, and bathroom. The six-item version was estimated with Samejima’s graded response model, and tested for differential item functioning by country. Three of the six items were invariant across countries, thus anchoring the scale to a common metric across countries. The six-item scale correlated with parental reported income groups in six out of eight countries. Findings support a revision to six items in the family affluence scale.     

High in vitro efficacy of Nyda® L, a pediculicide containing dimeticone

BACKGROUND: The therapy of pediculosis remains a common problem in clinical practice. As resistance to commonly used chemical pediculicides is constantly increasing, there is a need for new effective compounds. STUDY DESIGN: The efficacy of Nyda L, a new pediculicide containing a high concentration of dimeticone, was assessed in an in vitro trial and compared with three reference products (Hedrin containing 4% dimeticone, Lyclear containing 1% permethrin, and Prioderm containing 1% malathion) and a negative control group. Head lice were collected from heavily infested patients in a resource-poor community in Northeast Brazil, where no resistance against pediculicides has been reported thus far. In each of the five groups, 50 adult fully vital lice were tested. We used a dip test (immersing head lice in the undiluted products for 3 min, washing off products after 20 min). Using predefined criteria for mortality, the lice were monitored at different points in time, for a period of 24 h. RESULTS: Nyda L and Prioderm killed all head lice already after 5 min. The efficacy of Nyda L was better than of Lyclear. Lice treated with Hedrin resurrected after several hours and did not show a significantly higher mortality compared with the control group after 24 h. CONCLUSION: Nyda L can be regarded as a very efficacious pediculicidal compound, killing all lice in vitro within 5 min.     

MDM4 is a rational target for treating breast cancers with mutant p53

Mutation of the key tumour suppressor p53 defines a transition in the progression towards aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, the p53 mutation frequency exceeds 50% in triple‐negative BC. Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal‐like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells. We demonstrate that conditional knockdown (KD) of MDM4 provokes growth inhibition across a range of BC subtypes with mutant p53, including luminal, Her2⁺ and triple‐negative BCs. In vivo, MDM4 was shown to be crucial for the establishment and progression of tumours. This growth inhibition was mediated, at least in part, by the cell cycle inhibitor p27. Depletion of p27 together with MDM4 KD led to recovery of the proliferative capacity of cells that were growth‐inhibited by MDM4 KD alone. Consistently, we identified low levels of p27 expression in basal‐like tumours corresponding to high levels of MDM4 and p53. This predicts a signature for a subset of tumours that may be amenable to therapies targeted towards MDM4 and mutant p53. The therapeutic potential of MDM4 as a target in BC with mutant p53 was shown in vitro by use of a small‐molecule inhibitor. Overall, our study supports MDM4 as a novel therapeutic target for BC expressing mutant p53. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.