Fibrolipomatous hamartoma of the median nerve: A cause of acute bilateral carpal tunnel syndrome in a three-year-old child: A case report and comprehensive literature review

A three-year-old boy was investigated for inexplicable incessant crying. On examination, his left wrist was mildly swollen (three to four months) and sensitive. Exploration and carpal tunnel decompression of the left wrist with incisional biopsy was performed for the presence of a fusiform swelling intimately associated with the median nerve. Histopathology revealed the presence of enlarged nerve bundles admixed with mature fat cells and diffuse fibroblastic proliferation. Three months later, he underwent urgent contralateral carpal tunnel decompression for a similar presentation. The final diagnosis was bilateral fibrolipomatous hamartoma (FLH) of the median nerves causing acute bilateral compression neuropathy.FLH of the median nerve is an extremely unusual cause of acute bilateral carpal tunnel syndrome in a young child presenting with ‘incessant crying’. A comprehensive review of FLH including epidemiology, etiology, clinical presentation, differential diagnosis, imaging, pathology, treatment and prognosis is discussed.     

TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells

The molecular pathogenesis of the myeloid leukemias that frequently occur in patients with Fanconi anemia (FA) is not well defined. Hematopoietic stem cells bearing inactivating mutations of FA complementation group C (FANCC) are genetically unstable and hypersensitive to apoptotic cytokine cues including IFN-gamma and TNF-alpha, but neoplastic stem cell clones that arise frequently in vivo are resistant to these cytokines. Reasoning that the combination of genetic instability and cytokine hypersensitivity might create an environment supporting the emergence of leukemic stem cells, we tested the leukemia-promoting effects of TNF-alpha in murine stem cells. TNF-alpha exposure initially profoundly inhibited the growth of Fancc-/- stem cells. However, longer-term exposure of these cells promoted the outgrowth of cytogenetically abnormal clones that, upon transplantation into congenic WT mice, led to acute myelogenous leukemia. TNF-alpha induced ROS-dependent genetic instability in Fancc-/- but not in WT cells. The leukemic clones were TNF-alpha resistant but retained their characteristic hypersensitivity to mitomycin C and exhibited high levels of chromosomal instability. Expression of FANCC cDNA in Fancc-/- stem cells protected them from TNF-alpha-induced clonal evolution. We conclude that TNF-alpha exposure creates an environment in which somatically mutated preleukemic stem cell clones are selected and from which unaltered TNF-alpha-hypersensitive Fancc-/- stem cells are purged.     

Chlorotoxin: A Helpful Natural Scorpion Peptide to Diagnose Glioma and Fight Tumor Invasion

Chlorotoxin is a small 36 amino-acid peptide identified from the venom of the scorpion Leiurus quinquestriatus. Initially, chlorotoxin was used as a pharmacological tool to characterize chloride channels. While studying glioma-specific chloride currents, it was soon discovered that chlorotoxin possesses targeting properties towards cancer cells including glioma, melanoma, small cell lung carcinoma, neuroblastoma and medulloblastoma. The investigation of the mechanism of action of chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. Efforts on chlorotoxin-based applications focused on producing analogues helpful for glioma diagnosis, imaging and treatment. These efforts are welcome since gliomas are very aggressive brain cancers, close to impossible to cure with the current therapeutic arsenal. Among all the chlorotoxin-based strategies, the most promising one to enhance patient mean survival time appears to be the use of chlorotoxin as a targeting agent for the delivery of anti-tumor agents. Finally, the discovery of chlorotoxin has led to the screening of other scorpion venoms to identify chlorotoxin-like peptides. So far several new candidates have been identified. Only detailed research and clinical investigations will tell us if they share the same anti-tumor potential as chlorotoxin.     

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction

Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach.

Methods

Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39).

Results

Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1).

Conclusions

These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0532-0) contains supplementary material, which is available to authorized users.     

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients

Background: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. Objective: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin^®) and compare it with the innovator product Eprex^®, as a standard rHuEPO. Methods: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80–120 IU/kg/week in 2–3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. Results: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Conclusion: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.     

Numb 基因负性调节 CXCR4表达抑制膀胱癌细胞 BIU-87的增殖和迁移

目的：研究 Numb 基因对趋化因子受体4（CXCR4）表达的影响以及对膀胱癌细胞增殖和迁移的影响。方法实验分为3组：实验组（在膀胱癌细胞 BIU-87中转染 Numb-ORF 表达质粒）、阴性对照组（转染空载体）和空白对照组（未行转染处理）。使用荧光定量 PCR 和 Western blotting 检测各组细胞 Numb 和 CXCR4的表达。使用 MTS 法和 Transwell 小室法检测细胞增殖和迁移能力。结果实验组、阴性对照组和空白对照组中 Numb 基因表达水平分别为31.044±3.350、4.401±0.567和4.287±0.341,差异有统计学意义（F ＝183.418,P ＝0.000）;实验组、阴性对照组和空白对照组的 CXCR4表达水平分别为0.344±0.167、0.996±0.148和1.010±0.106,差异有统计学意义（ F ＝21.355,P ＝0.002）。细胞增殖检测中实验组、阴性对照组和空白对照组的48 h 吸光度值分别为0.615±0.057、0.987±0.063和0.957±0.066,差异有统计学意义（F ＝33.210,P ＝0.001）。迁移实验中,实验组、阴性对照组和空白对照组的穿膜细胞数分别为（164.667±19.858）个、（670.133±38.760）个和（667.533±27.610）个,差异有统计学意义（F ＝286.788,P ＝0.000）。结论 Numb 可能通过负性调节CXCR4表达抑制膀胱癌细胞的增殖和迁移。     

Pain interference and incident mood,anxiety, and substance-use disorders: Findings from a representative sample of men and women in the general population

To examine gender differences in the longitudinal relationship between past-month pain interference and incident mood, anxiety, and substance-use disorders, chi-square tests and binomial logistic regression analyses were performed on data obtained from the National Epidemiologic Survey on Alcohol and Related Conditions from 34,465 adult respondents (47.9% men; 52.1% women) who completed waves 1 (2000–2001) and 2 (2004–2005) data collection. Models were adjusted for potentially confounding factors (i.e., age, race, marital status, educational level, employment, household income, number of stressful life events, number of general medical conditions, and wave-1 psychopathology). Respondents were categorized at wave 1 according to their past-month level of pain interference (i.e., no or low pain interference, moderate pain interference, severe pain interference). Moderate and severe pain interference (as compared to no or low pain interference) in male and female respondents was associated with the incidence of several psychiatric disorders. A stronger relationship was observed in male respondents as compared to female ones between past-month moderate pain interference and a new onset of any mood disorder (OR = 1.57, p = 0.03) and major depressive disorder (OR = 1.60, p = 0.03), and between past-month severe pain interference and a new onset of alcohol abuse or dependence (OR = 1.69, p = 0.045) and nicotine dependence (OR = 1.48, p = 0.04). These findings suggest that providers should consider screening patients with past-month moderate or severe pain interference for mood, anxiety, and substance-use problems and monitor the possible development of subsequent comorbid psychiatric disorders.     

Differences in gambling problem severity and gambling and health/functioning characteristics among Asian-American and Caucasian high-school students

Studies of Asian-American adults have found high estimates of problematic gambling. However, little is known about gambling behaviors and associated measures among Asian-American adolescents. This study examined gambling perceptions and behaviors and health/functioning characteristics stratified by problem-gambling severity and Asian-American and Caucasian race using cross-sectional survey data of 121 Asian-American and 1659 Caucasian high-school students. Asian-American and Caucasian adolescents significantly differed on problem-gambling severity, with Asian-American adolescents more often reporting not gambling (24.8% vs. 16.4%), but when they did report gambling, they showed higher levels of at-risk/problem gambling (30.6% vs. 26.4%). Parental approval or disapproval of adolescent gambling also significantly differed between races, with Asian-American adolescents more likely to perceive both parental disapproval (50.0% vs. 38.2%) and approval (19.3% vs. 9.6%) of gambling. Asian-American adolescents were also more likely to express concern about gambling among close family members (25.2% vs. 11.6%). Among Asian-American adolescents, stronger associations were observed between at-risk/problem gambling and smoking cigarettes (interaction odds ratio=12.6). In summary, differences in problem-gambling severity and gambling perceptions indicate possible cultural differences in familial attitudes towards gambling. Stronger links between cigarette smoking and risky/problematic gambling amongst Asian-American adolescents suggest that prevention and treatment efforts targeting youth addictions consider cultural differences.