MicroRNAs are a class of endogenous single strand non-coding RNAs that are involved in many important physiological and pathological processes. The purpose of this study was to examine the expression levels of miR-497 in human breast cancer and its function in MDA-MB-231 breast cancer cells.
Quantitative polymerase chain reaction was used to measure the expression levels of miR-497 in 40 breast cancer specimens and adjacent normal breast tissues. MTT assays, colony formation assays, wound healing assays, transwell assays and cell cycle assays were used to explore the potential function of miR-497 in MDA-MB-231 breast cancer cells. Dual-luciferase reporter assays were performed to analyze the regulation of putative target of miR-497, and western blot assays were used to validate the dual-luciferase results.
The expression of miR-497 in breast cancer specimens was lower than adjacent normal tissues (P < 0.05). Overexpression of miR-497 inhibited cellular growth, suppressed cellular migration and invasion, and caused a G1 arrest. Dual-luciferase reporter assays showed that miR-497 binds the 3′-untranslated region (3′-UTR) of cyclin E1, suggesting that cyclin E1 is a direct target of miR-497. Western blot assays confirmed that overexpression of miR-497 reduced cyclin E1 protein levels.
MiR-497 may act as a tumor suppressor gene in breast cancer. Inhibited cellular growth, suppressed cellular migration and invasion, and G1 cell cycle arrest were observed upon overexpression of miR-497 in cells, possibly by targeting cyclin E1. These results indicate miR-497 could be considered a therapeutic target for the development of treatment for breast cancer.
MiR-497; Breast cancer; Cyclin E1
Background: NIN/RPN Binding protein 1 homologue (NOBp1), encoded by NOB1 gene, was reported to play an essential role in the oncogenesis and prognosis of carcinomas. We conducted a study to reveal its expression and clinical significance in breast infiltrating ductal carcinoma. Methods: To explore the relationship between NOB1 expression and the clinical TNM (cTNM), 162 patients who undergone surgery were involved in the study. Compared to healthy tissues, abnormal localization and higher level of NOB1 in tumor cells was observed by Immunohistochemistry staining. Real-time PCR and western-blotting verified the up-regulation of NOB1 in carcinoma individuals. Results: A significant correlation between high level of NOB1 and the T stage, lymph node metastasis and cTNM was shown. Furthermore, patients with higher level of NOB1 predicted a declined overall survival (OS). Notably, multivariate analyses by Cox’s proportional hazard model revealed that expression of NOB1 was an independent prognostic factor in breast infiltrating ductal carcinoma. Conclusions: In summary, our present study clarify that the aberrant expression of NOB1 in breast infiltrating ductal carcinoma is possibly involved with tumorigenesis and development, and the NOB1 protein could act as a potential biomarker for prognosis assessment of breast infiltrating ductal carcinoma. Related mechanism is worthy of further investigation.
Breast cancer; NOB1 protein; immunohistochemistry; tissue microarray
Techniques for expanding skin and soft tissue are widely used to repair damaged areas since they facilitate the provision of new, additional skin tissue with similar quality, texture and color to that surrounding the defective area. Conventional expansion techniques involve placing expanders under the normal skin adjacent to a lesion. However, these techniques may involve additional incisions, complications with blood supply and ‘dog-ear’ deformities and may result in a low utilization rate of the expanded tissue. When reconstructing small defects that may not be sutured directly, these shortcomings, particularly the requirement to make additional incisions, limit the application of conventional techniques. The current study presents a novel approach to expansion called the ‘expansion in-situ’ technique. In this technique, the lesion is used as the center for expansion and expanders of optimal size are implanted under the lesion and surrounding normal soft tissue. Following expansion, the damaged area is excised directly. In order to avoid poor healing of the incision made during expander implantation, the overlapping suturing of both cut sides is conducted. This enlarges the contact area of both sides of the incision, thereby avoiding incision dehiscence and increasing wound healing during the expansion process. Between August 2006 and July 2011, the expansion in-situ technique was applied in 10 cases involving either nevus excision or scar removal. All 10 cases were treated successfully. Five of the cases were followed up over 1–3 years. The ‘expansion in-situ’ technique is likely to be useful for avoiding additional incisions and improving the utilization rate of expanded skin flaps.
soft tissue expansion; incision dehiscence; expansion in-situ; additional incision; cicatrix
MicroRNAs (miRNAs) are small, non-coding RNAs (20–24 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. The aim of this study was to investigate the expression pattern of microRNA-26b (miR-26b) in human breast cancer, and its potential role in disease pathogenesis.
Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-26b in 38 breast cancer specimens and adjacent normal breast tissues. MTT assays were conducted to explore the impact of miR-26b overexpression on the proliferation of human MDA-MB-231 breast cancer cells. Luciferase reporter assays were employed to validate regulation of a putative target of miR-26b. The effect of modulating miR-26b on endogenous levels of this target were subsequently confirmed via qRT-PCR and Western blot.
MiR-26b expression was relatively decreased in breast cancer specimens compared with adjacent normal tissues (P<0.01). Overexpression of miR-26b suppressed MDA-MB-231 cell growth. Luciferase assays using a reporter carrying a putative miR-26b target site in the 3' untranslated region of PTGS2 revealed that miR-26b directly targets PTGS2. Overexpression of miR-26b led to downregulation of PTGS2 at the mRNA and protein level, as assessed by qRT-PCR and Western blot. Targeted knockdown of PTGS2 by siRNA significantly inhibited the proliferation of MDA-MB-231 breast cancer cells.
MiR-26b may act as a tumor suppressor in breast cancer. The overexpression of miR-26b inhibits cellular growth by targeting PTGS2, suggesting its use as a potential therapeutic target for breast cancer.
MiR-26b; Proliferation; PTGS2; Breast cancer
We aimed to report our successful use of frontalis muscle flap suspension for the correction of congenital blepharoptosis in early age children.
This retrospective study included 61 early age children (41 boys, 20 girls) with an average age of 6 years (range, 3–10 years) with congenital blepharoptosis who received surgery during the period from March 2007 to January 2011. There were 39 cases of unilateral blepharoptosis and 22 cases of bilateral blepharoptosis, thus a total of 83 eyes were affected. If patient had bilateral blepharoptosis, both eyes were operated on in the same surgery. Patients were followed for 3 months to 5 years. The procedure was performed without complications in all cases.
The postoperative healing grade was good in 81 eyes (97.6%); the correction of blepharoptosis was satisfactory, the double eyelid folds were natural and aesthetic, the eyelid position and the curvature were ideal, and the eyes were bilaterally symmetrical. The postoperative healing grade was fair in 2 eyes (2.4%); blepharoptosis was improved compared with that before surgery. At discharge, lagophthalmos was noted in 10 eyes of which 4 cases resolved by the last follow-up. The remaining 6 cases were mild. Eleven eyes received reoperation for residual ptosis after the first surgery. The curvature of the palpebral margin was not natural in 4 eyes. These unnatural curvature possibly was caused by an excessively low lateral fixation point or postoperative avulsion.
Frontalis muscle flap suspension under general anesthesia for the correction of congenital blepharoptosis in early age children can achieve good surgical results.
Successful eyelid reconstructions have been reported when using an axial nasal chondromucosal flap based on the dorsal nasal artery. The present study aimed to present a detailed anatomical description of the blood supply of the lateral nasal region and the angular artery, in order to propose the angular vessels as a new vascular pedicle for the island nasal chondromucosal flap. A total of 11 cadavers (22 hemi-faces) were examined. Observations with regard to the origin, course and distribution patterns of the angular artery were recorded. Based on the anatomical study findings, the angular vessels were proposed as a vascular source for the island nasal chondromucosal flap. Observations with regard to the varying origins of the angular artery were categorized into four types. The course of the angular artery along the nasojugal fold was constant. The angular artery branched off into the upper two-thirds of the lateral nasal region and anastomosed with the other vascular branches on the nasal dorsum. Clinically, reconstruction of a full-thickness defect of the lower eyelid was successfully performed by using this composite flap based on the angular vessels and an adjacent orbicularis oculi myocutaneous flap. Satisfactory esthetic outcomes were obtained for the donor and recipient sites. The angular artery is a good vascular source for an island nasal chondromucosal flap. The flap may be created safely and successfully in clinic. Island nasal chondromucosal flaps and nasolabial groove skin flaps based on the angular vessels may be designed simultaneously for use on full-thickness defects of the eyelid.
eyelid reconstruction; chondromucosal flap; angular vessels
Existing methods for predicting protein solubility on overexpression in Escherichia coli advance performance by using ensemble classifiers such as two-stage support vector machine (SVM) based classifiers and a number of feature types such as physicochemical properties, amino acid and dipeptide composition, accompanied with feature selection. It is desirable to develop a simple and easily interpretable method for predicting protein solubility, compared to existing complex SVM-based methods.
This study proposes a novel scoring card method (SCM) by using dipeptide composition only to estimate solubility scores of sequences for predicting protein solubility. SCM calculates the propensities of 400 individual dipeptides to be soluble using statistic discrimination between soluble and insoluble proteins of a training data set. Consequently, the propensity scores of all dipeptides are further optimized using an intelligent genetic algorithm. The solubility score of a sequence is determined by the weighted sum of all propensity scores and dipeptide composition. To evaluate SCM by performance comparisons, four data sets with different sizes and variation degrees of experimental conditions were used. The results show that the simple method SCM with interpretable propensities of dipeptides has promising performance, compared with existing SVM-based ensemble methods with a number of feature types. Furthermore, the propensities of dipeptides and solubility scores of sequences can provide insights to protein solubility. For example, the analysis of dipeptide scores shows high propensity of α-helix structure and thermophilic proteins to be soluble.
The propensities of individual dipeptides to be soluble are varied for proteins under altered experimental conditions. For accurately predicting protein solubility using SCM, it is better to customize the score card of dipeptide propensities by using a training data set under the same specified experimental conditions. The proposed method SCM with solubility scores and dipeptide propensities can be easily applied to the protein function prediction problems that dipeptide composition features play an important role.
The used datasets, source codes of SCM, and supplementary files are available at http://iclab.life.nctu.edu.tw/SCM/.
Confronting developmental tasks and challenges associated with bridging two different cultures, Asian American adolescent girls face increasing risks for substance use. Identifying risk and protective factors in this population is essential, particularly when those factors can inform preventive programs. Guided by family interaction theory, the present cross-sectional study explored the associations of psychological and familial factors with use of alcohol, prescription drugs, and other drugs among early-adolescent Asian American girls. Between August 2007 and March 2008, 135 pairs of Asian American girls (mean age 13.21 years, SD = 0.90) and their mothers (mean age 39.86 years, SD = 6.99) were recruited from 19 states that had significant Asian populations. Girls and mothers each completed an online survey. Relative to girls who did not use substances, girls who did had higher levels of depressive symptoms, perceived peer substance use, and maternal substance use. Multiple logistic regression modeling revealed that they also had significantly lower levels of body satisfaction, problem-solving ability, parental monitoring, mother-daughter communication, family involvement, and family rules about substance use. Household composition, acculturation, and academic achievement were not associated with girls’ substance use. These findings point to directions for substance abuse prevention programming among Asian American girls.
Asian Americans; substance use; female; adolescents; risk factors; family
Background: Ras signaling is known to be critical for tumor progression.
Results: Ras-PI3K regulates H3K56 acetylation (H3K56ac) via the MDM2-dependent degradation of CBP/p300. H3K56ac is revealed to be associated with the transcription, proliferation, and migration of tumor cells.
Conclusion: H3K56 acetylation is a critical component of the oncogenic Ras-PI3K pathway.
Significance: The Ras-PI3K-AKT-H3K56ac pathway is a potential target for cancer therapy.
It is well established that the small GTPase Ras promotes tumor initiation by activating at least three different mediators: Raf, PI3K, and Ras-like (Ral) guanine nucleotide exchange factors. However, the exact mechanisms that underlie these different Ras signaling pathways, which are involved in tumor progression, remain to be elucidated. In this study, we report that the Ras-PI3K pathway, but not Raf or the Ral guanine nucleotide exchange factors, specifically targets the acetylation of H3 at lysine 56 (H3K56ac), thereby regulating tumor cell activity. We demonstrate that the Ras-PI3K-induced reduction in H3K56ac is associated with the proliferation and migration of tumor cells by targeting the transcription of tumor-associated genes. The depletion of the histone deacetyltransferases Sirt1 and Sirt2 rescues the Ras-PI3K-induced decrease in H3K56ac, gene transcription, tumor cell proliferation, and tumor cell migration. Furthermore, we demonstrate that the Ras-PI3K-AKT pathway regulates H3K56ac via the MDM2-dependent degradation of CREB-binding protein/p300. Taken together, the results of this study demonstrate that the Ras-PI3K signaling pathway targets specific epigenetic modifications in tumor cells.
CBP; Epigenetics; Histone Modification; p300; Phosphatidylinositol 3-Kinase; Ras; Signal Transduction; MDM2; Histone Acetylation
Rarely has substance use prevention programming targeted Asian American adolescents. Using a focus group methodology, we explored perceptions of substance use and preferences for prevention programming among 31 Asian American adolescents in New York City. Participants considered substance use common in the community. Factors contributing to substance use among Asian American adolescents (e.g., peer pressure, pressure to achieve, family factors, and community influence) were identified, and the need for prevention programs tailored for the Asian American community was highlighted. Participants discussed preferred program content, delivery settings, and recruitment and retention strategies. Despite the favorable attitude for family-based prevention programming, participants raised potential issues concerning the feasibility of such a program. Study findings facilitate understanding of Asian American adolescents’ substance use behavior and shed light on prevention program development for this underserved population.
Asian Americans; adolescents; substance use; prevention; model minority; parents
Since the introduction of the theory of tumour stem cells (TSCs), the liver cancer stem cell (LCSC)-like cells have become one of the focuses in the research on liver cancer.
Materials and methods.
In this study, CD90+ cells were applied as the possible LCSC-like cells, and the miRNA and gene expression were analyzed in the CD90+ HepG2 cells. The pilot study showed miR-548c-5p exerted potential effect on the CD90+ HepG2 cells and was thereafter applied for the further study. CD90+ HepG2 cells were assigned to miR-548c-5p mimic transfection group and control group. MTT assay was performed to detect the proliferation of CD90+ HepG2 cells. The migration and invasion abilities were examined by wound healing assay and transwell migration assay, respectively. A detection of apoptosis was performed by fluorescence microscopy.
Our results showed that caspase-3 and bcl-2 were down-regulated while caspase-8 was up-regulated in the CD90+ HepG2 cells. Moreover, the miR-548c-5p transfection could down-regulate the expression of β-catenin, Tg737, bcl-2, bcl-XL, and caspase-3, inhibit the proliferation, migration and invasion and promote the apoptosis of the CD90+ HepG2 cells.
Our findings indicate the imbalance between apoptosis and anti-apoptosis in the LCSC-like cells, which influence the biological features of LCSC-like cells. miRNA plays a regulatory role in the LCSC-like cells among which miR-548c-5p might be a suppressor.
liver cancer stem cells; miR-548c-5p; apoptosis; NF-κB, β-catenin
Pancreaticobiliary maljunction (PBM) is often associated with congenital choledochal cyst, protein plugs and pancreatitis. Early diagnosis and timely treatment largely depend on imaging. We assessed a series of PBM in children, comparing imaging procedure with histological and pathological findings with regard to diagnosis.
A retrospective analysis was conducted in 75 pediatric patients with PBM. PBM was defined as common channel at >5 mm. Two radiologists assess the shape of the bile duct and gallbladder, pancreatitis, surgical pathology, symptom profiles, operative notes and pathological records were compared with the imaging findings.
Dilatation of the bile duct was detected in 45 subjects out of the 46 subjects who underwent computed tomography (CT) and nine was diagnosis as PBM. Forty out of 41 subjects were revealed bile duct dilatation in ultrasonography (US). Bile duct dilatation was seen in 59 out of 60 subjects receiving magnetic resonance cholangiopancreatography (MRCP) and 39 were diagnosed as PBM. Seventy-four out of 75 subjects successfully underwent intraoperative cholangiography (IOC); a diagnosis of PBM was established in 60 cases based on IOC alone. The diagnosis rate of pediatric PBM varied significantly among the four groups (P < 0.0001). Pair-wise comparison showed a significant difference between the groups of MRCP and CT (P < 0.0001), MRCP and US (P < 0.0001), IOC and CT (P < 0.0001), IOC and US (P < 0.0001), CT and US (P = 0.0027), and there is no significant difference between the groups of IOC and MRCP (P = 0.0502).
US, IOC, CT and MRCP are valuable in showing dilatation of the bile duct and complications in pediatric PBM. MRCP is non-invasive, gives clear views of the pancreaticobiliary junction and should be the first choice for the diagnosis of PBM in children.
Pancreaticobiliary maljunction; Pediatric; Imaging; Intraoperative cholangiography
Maintaining an appropriate cellular concentration of p53 is critical for cell survival and normal development in various organisms. In this study, we provide evidence that the human E2 ubiquitin-conjugating enzyme RAD6 plays a critical role in regulating p53 protein levels under both normal and stress conditions. Knockdown and overexpression of RAD6 affected p53 turnover and transcription. We showed that RAD6 can form a ternary complex with MDM2 and p53 that contributes to the degradation of p53. Chromatin immunoprecipitation (ChIP) analysis showed that RAD6 also binds to the promoter and coding regions of the p53 gene and modulates the levels of H3K4 and K79 methylation on local chromatin. When the cells were exposed to stress stimuli, the RAD6-MDM2-p53 ternary complex was disrupted; RAD6 was then recruited to the chromatin of the p53 gene, resulting in an increase in histone methylation and p53 transcription. Further studies showed that stress-induced p53 transcriptional activation, cell apoptosis, and disrupted cell cycle progression are all RAD6 dependent. Overall, this work demonstrates that RAD6 regulates p53 levels in a “yin-yang” manner through a combination of two distinct mechanisms in mammalian cells.
Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in Northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: −13910*C/T. To determine whether the −13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the −13910*T SNP or the ancestral −13910*C SNP cloned upstream of a 2 kb rat lactase gene promoter in a luciferase reporter construct. We previously reported that the 2 kb rat lactase promoter directs a post-weaning decline of luciferase transgene expression similar to that of the endogenous lactase gene. In the present study, the post-weaning decline directed by the rat lactase promoter is impeded by addition of the −13910*T SNP human DNA fragment, but not by addition of the −13910*C ancestral SNP fragment. Persistence of transgene expression associated with the −13910*T SNP represents the first in vivo data in support of a functional role for the −13910*T SNP in mediating the human lactase persistence phenotype.
lactase; gene regulation; SNP; transgenic mice
microRNAs are a small class of non-coding RNAs with a critical role in the tumorigenesis and maintenance of breast cancer through binding to the 3′-untranslated regions of target mRNAs, which causes a block of translation and/or mRNA degradation. The purpose of this study was to investigate the expression of microRNA-497 (miR-497) as well as its potential role in human breast cancer. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the expression pattern of miR-497 in breast cancer and normal breast tissues. Correlation analysis was conducted to characterize the association of miR-497 expression abnormality with pathological factors. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human MCF-7 breast cancer cells. RT-PCR and Western blot analysis were employed to validate the downstream targets of miR-497. miR-497 expression was relatively decreased in breast cancer specimens and negatively correlated with TNM stage, lymphatic metastasis, tumor size and human epidermal growth factor receptor-2 (P<0.01). On the contrary, no correlation was found with estrogen receptor, progesterone receptor and p53 status. Functional assays revealed that miR-497 suppressed cellular growth, increased the percentage of early apoptotic cells and initiated G0/G1 cell phase arrest of MCF-7 cancer cells. RT-PCR and Western blot analysis data indicated that the overexpression of miR-497 resulted in the down-regulation of Bcl-w at the mRNA and protein levels. miR-497 may serve as a tumor suppressor gene in breast cancer. The Up-regulation of miR-497 expression causes cellular growth inhibition and apoptotic enhancement, as well as G0/ G1 phase arrest, suggesting its use as a potential therapeutic target for the treatment of breast cancer in the future.
breast cancer; microRNA-497; Bcl-w; cell proliferation; cell apoptosis
The relatively recent discovery of microRNAs has added a completely new dimension to the study of the regulation of tumor cells, but how they control cell behavior remains largely elusive. HepG2 cells were assigned to the miR-1301 group and the control group. RT-PCR, Western blotting, wound healing, the Transwell chamber migration and MTT assays, and apoptosis detection assays were used to analyze cell behavior of HepG2 cells after miR-1301 mimic transfection. Our study showed that miR-1301 was downregulated in HepG2 cells, and that miR-1301 inhibited migration and invasion of HepG2 cells and promoted cellular apoptosis after transfection with miR-1301 mimics. In addition, p53 mRNA and p53 protein expression was upregulated, and Bcl-2 and Bcl-xL mRNA and protein expression was downregulated in the miR-1301 group. These results indicate that miR-1301 may be an inhibitor of tumorigenesis in HepG2 cells.
microRNA-1301; tumor; invasion; apoptosis; HepG2 cell
Introduction: The diagnostic value of colour Doppler sonography for the detection of blood flow in intussusception is questionable. The purpose of this study was to evaluate plain radiography in the assessment of vascular compromise in children with intussusception.
Material and methods
The hospital notes of 1,119 paediatric cases of intussusception who presented between January 2007 and February 2008 were retrospectively analysed. Informed consent was given by the parents before the air enema and this study was approved by the hospital ethics committee. Overall, the plain abdominal X-rays of 190 cases were assessed independently by two experienced radiologists, and disagreements were settled by discussion. Symptom profiles, operative notes and pathological records were compared to plain radiography. SAS V8.1 was used for the analysis.
Of the 190 patients, 30 cases had vascular compromise on plain films, as shown by the “coffee-bean” sign or “banana” sign. There was a paucity of gas in 36 cases, a quadrant-specific gas pattern in 51 cases, and the film showed a mass in 73 cases. Statistical analysis that compared signs on plain radiography signs and symptom onset showed a significant difference. Ninety-five cases were irreducible by air enema and required surgical intervention. The location of these intussusceptions were ileo-ileal-colic (n = 44), ileo-colic (n = 25), ileo-ileal (n = 14), ileo-caecal (n = 10), and ileo-colic-colic (n = 2). Eleven cases had intestinal necrosis and underwent resection of the necrotic bowel.
The signs of intussusception on plain radiography were significant during the clinical assessment of children with secondary ischaemic bowel. The radiological findings were shown to have a high concordance with pathology in the assessment of intussusception.The diagnostic value of colour Doppler sonography for the detection of blood flow in intussusception is questionable. The purpose of this study was to evaluate plain radiography in the assessment of vascular compromise in children with intussusception.
paediatric; intussusception; plain radiography; vascular compromise
This study examined the efficacy and generalizability of a family-oriented, web-based substance use prevention program to young Asian-American adolescent girls.
Between September and December 2007, 108 Asian-American girls aged 10-14 years and their mothers were recruited through online advertisements and from community service agencies. Mother-daughter dyads were randomly assigned to an intervention arm or to a test-only control arm. Following pretest measurement, intervention-arm dyads completed a 9-session web-based substance use prevention program. Guided by family interaction theory, the program aimed to improve girls' psychological states, strengthen substance use prevention skills, increase mother-daughter interactions, enhance maternal monitoring, and prevent girls' substance use. Study outcomes were assessed using generalized estimating equations.
At posttest, relative to control-arm girls, intervention-arm girls showed less depressed mood; reported improved self-efficacy and refusal skills; had higher levels of mother-daughter closeness, mother-daughter communication, and maternal monitoring; and reported more family rules against substance use. Intervention-arm girls also reported fewer instances of alcohol, marijuana, and illicit prescription drug use, and expressed lower intentions to use substances in the future.
A family-oriented, web-based substance use prevention program was efficacious in preventing substance use behavior among early Asian-American adolescent girls.
Asian Americans; adolescent; female; family; prevention; substance use; computer; web-based
This 2008 study involved 546 Black- and Hispanic-American adolescent girls and their mothers from New York, New Jersey, and Connecticut. Participants provided self-report data. Analysis of covariance indicated that the experimental intervention reduced risk factors, improved protective factors, and lowered girls' alcohol use and their future intentions to use substances. The study supports the value of computer-based and gender-specific interventions that involve girls and mothers. Future work needs to replicate and strengthen study results. Research support came from the National Institute on Drug Abuse within the National Institutes of Health of the United States Public Health Service.
Drug use; adolescent girls; computer-delivered prevention programming; family intervention
This study aimed to determine the miRNA profile in breast cancer stem cells (BCSCs) and to explore the functions of characteristic BCSC miRNAs.
We isolated ESA+CD44+CD24-/low BCSCs from MCF-7 cells using fluorescence-activated cell sorting (FACS). A human breast cancer xenograft assay was performed to validate the stem cell properties of the isolated cells, and microarray analysis was performed to screen for BCSC-related miRNAs. These BCSC-related miRNAs were selected for bioinformatic analysis and target prediction using online software programs.
The ESA+CD44+CD24-/low cells had up to 100- to 1000-fold greater tumor-initiating capability than the MCF-7 cells. Tumors initiated from the ESA+CD44+CD24-/low cells were included of luminal epithelial and myoepithelial cells, indicating stem cell properties. We also obtained miRNA profiles of ESA+CD44+CD24-/low BCSCs. Most of the possible targets of potential tumorigenesis-related miRNAs were oncogenes, anti-oncogenes or regulatory genes.
We identified a subset of miRNAs that were differentially expressed in BCSCs, providing a starting point to explore the functions of these miRNAs. Evaluating characteristic BCSC miRNAs represents a new method for studying breast cancer-initiating cells and developing therapeutic strategies aimed at eradicating the tumorigenic subpopulation of cells in breast cancer.
Guided by family interaction theory, this study examined the influences of psychological, peer, and familial processes on alcohol use among young adolescent girls and assessed the contributions of familial factors. An ethnically-diverse sample of 1187 pairs of girls (M age = 12.83 years) and their mothers completed surveys online. Questionnaires assessed girls’ lifetime and recent alcohol use, as well as girls’ demographic, psychological, peer, and family characteristics. Hierarchical logistic regression models showed that although girls’ drinking was associated with a number of psychological and peer factors, the contributions of family domain variables to girls’ drinking were above and beyond that of psychological and peer factors. The interaction analyses further highlighted that having family rules, high family involvement, and greater family communication may offset risks in psychological and peer domains. Study findings underscore the multifaceted etiology of drinking among young adolescent girls and assert the crucial roles of familial processes. Prevention programs should be integrative, target processes at multiple domains, and include work with parents.
Early adolescence; Alcohol; Underage drinking; Parents; Parenting; Females; Prevention
This study tested a computerized gender-specific, parent-involvement intervention program grounded in family interaction theory and aimed at preventing substance use among adolescent girls. Following program delivery and 1 year later, girls randomly assigned to the intervention arm improved more than girls in a control arm on variables associated with reduced risks for substance use, including communication with their mothers, knowledge of family rules about substance use, awareness of parental monitoring of their discretionary time, non-acceptance of peer substance use, problem-solving skills, and ability to refuse peer pressure to use substances. Relative to control-arm girls, those in the intervention arm also reported less 30-day use of alcohol and marijuana and lower intentions to smoke, drink, and take illicit drugs in the future. Girls’ mothers in the intervention arm reported greater improvements after the program and relative to control-arm mothers in their communication with their daughters, establishment of family rules about substance use, and monitoring of their daughters’ discretionary time. Study findings lend support to the potential of gender-specific, parent-involvement, and computerized approaches to preventing substance use among adolescent girls.
adolescent girls; substance use; prevention programming; family approaches
To test a computer-delivered program for preventing substance use among adolescent girls.
Randomly, 916 girls aged 12.76 ± 1.0 years and their mothers were assigned to an intervention arm or to a test-only control arm. Intervention-arm dyads engaged in exercises to improve the mother-daughter relationship, build girls’ substance use prevention skills, and reduce associated risk factors. Study outcomes were girls’ and mothers’ substance use and mediator variables related to girls’ substance use risk and protective factors. The study was conducted between September 2006 and February 2009 with participants from greater New York City, including southern Connecticut and eastern New Jersey.
At 2-year follow-up and relative to control-arm girls, intervention-arm girls reported lower relevant risk factors and higher protective factors as well as less past 30-day use of alcohol (p< 0.006), marijuana (p<0.016), illicit prescription drugs (p<0.03), and inhalants (p<0.024). Intervention-arm mothers showed more positive 2-year outcomes than control-arm mothers on variables linked with reduced risks of substance use among their daughters, and mothers reported lower rates of weekly alcohol consumption (p<0.0001).
A computer-delivered prevention program for adolescent girls and their mothers was effective in changing girls’ risk and protective factors and girls’ and mothers’ substance use behavior.
Adolescents; substance use; prevention programming; computerized approaches; family involvement