Efficacy of an Internet-based depression intervention to improve rates of treatment in adolescent mothers.

Approximately 400,000 adolescents give birth in the USA annually. Although one-half experience depressive symptoms, less than 25% comply with referrals for depression evaluation and treatment. The current study tested the effectiveness of an Internet-based depression intervention on seeking depression treatment. Based upon the theory of planned behavior (TPB), the intervention included vignettes, questions and answers, and resources. Before the intervention, immediately after the intervention, and 2 weeks later the adolescent mothers (n = 151) answered questions related to TPB variables and depression treatment. Data were compared to adolescent mothers (n = 138) in the control group. Data were collected in community organizations or home visits for the control group. Adolescent mothers in the intervention group answered questions and completed the intervention from a computer of their choice. The adolescents were primarily African American (89.2%), less than high school educated (51.7%), had given birth in last year (97.1%), with a mean age 18.2 years. The intervention led to significant changes in attitude, perceived control, intention to seek mental health treatment, and actually seeking depression treatment. Untreated postpartum depression dramatically impacts a mother's relationship with her child, her functioning at work and school, health care-seeking behaviors, mothering skills, and her development as well as the development of her child. An Internet-based depression intervention is an inexpensive method to increase rates of depression treatment.

NADPH oxidase NOX4 supports renal tumorigenesis by promoting the expression and nuclear accumulation of HIF2α.

Most sporadically occurring renal tumors include a functional loss of the tumor suppressor von Hippel Lindau (VHL). Development of VHL-deficient renal cell carcinoma (RCC) relies upon activation of the hypoxia-inducible factor-2α (HIF2α), a master transcriptional regulator of genes that drive diverse processes, including angiogenesis, proliferation, and anaerobic metabolism. In determining the critical functions for HIF2α expression in RCC cells, the NADPH oxidase NOX4 has been identified, but the pathogenic contributions of NOX4 to RCC have not been evaluated directly. Here, we report that NOX4 silencing in VHL-deficient RCC cells abrogates cell branching, invasion, colony formation, and growth in a murine xenograft model RCC. These alterations were phenocopied by treatment of the superoxide scavenger, TEMPOL, or by overexpression of manganese superoxide dismutase or catalase. Notably, NOX4 silencing or superoxide scavenging was sufficient to block nuclear accumulation of HIF2α in RCC cells. Our results offer direct evidence that NOX4 is critical for renal tumorigenesis and they show how NOX4 suppression and VHL re-expression in VHL-deficient RCC cells are genetically synonymous, supporting development of therapeutic regimens aimed at NOX4 blockade.

Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression.

Cell adhesion molecules (CADMs) comprise a protein family whose functions include maintenance of cell polarity and tumor suppression. In this report, we show that the CADM2 gene is repressed in human clear renal cell carcinoma by DNA promoter hypermethylation and/or loss of heterozygosity. Moreover, the loss of CADM2 expression is associated with a higher tumor pathology stage (p<0.05). The re-expression of CADM2 in the renal cancer cell line 786-O significantly suppressed tumor cell growth in vitro and in mouse xenografts by a G1 phase cell cycle arrest and the induction of apoptosis. Lentivirus-mediated CADM2 expression also significantly suppressed cancer cell anchorage-independent growth and invasion. Furthermore, the inhibition of endogenous CADM2 expression using siRNAs induced a tumorigenic phenotype in polarized non-tumorigenic MDCK cells. Thus, we conclude that CADM2 functions as a novel tumor suppressor and may serve as a potential therapeutic target for human renal cell carcinoma.

Deficiency of DNA repair nuclease ERCC1-XPF promotes prostate cancer progression in a tissue recombination model.

BACKGROUND: The excision repair cross complementing (ERCC1) gene product plays a vital role in the nucleotide excision repair (NER) and DNA interstrand crosslink repair pathways, which protect the genome from mutations and chromosomal aberrations, respectively. Genetic deletion of Ercc1 in the mouse causes dramatically accelerated aging. We examined the effect of Ercc1 deletion in the development of prostate cancer in a prostate recapitulation model as Ercc1 deficient mice die within four weeks of birth. METHODS: Prostate tissues from Ercc1(-/-) mice or wild-type littermates were combined with embryonic rat urogenital mesenchyme and grown as renal grafts for a total of 8, 16, and 24 weeks before histological, expression and proliferative evaluation. RESULTS: Invasive adenocarcinoma was observed in Ercc1(-/-) tissue recombinants but not wild-type as early as 8 weeks post-grafting. PIN-like lesions in Ercc1(-/-) tissue recombinants had more cytologic and architectural atypia than wild-type (P = 0.02, P = 0.0065, and P = 0.0003 at the 8, 16, and 24 weeks, respectively), as well as more proliferative cells (P = 0.022 and P = 0.033 at 8 and 16 weeks, respectively). With serial grafting, Ercc1(-/-) tissue recombinants progressed to a more severe histopathological phenotype more rapidly than wild-type (P = 0.011). CONCLUSIONS: Results show that ERCC1 and by implication the NER and/or interstrand crosslink repair mechanisms protect against prostate carcinogenesis and mutations or polymorphisms affecting these DNA repair pathways may predispose prostate epithelial cells to transformation.

Measurement of the thickness and volume of adherent cells using transmission-through-dye microscopy.

Cell volume is one of the basic characteristics of a cell and is being extensively studied in relationship to a variety of processes, such as proliferation, apoptosis, fertility, or locomotion. At the same time, its measurement under a microscope has not been well developed. The method we propose uses negative transmission contrast rendered to cells by a strongly absorbing dye present in the extracellular medium. Cells are placed in a shallow compartment, and a nontoxic and cell-impermeant dye, such as acid blue 9, is added to the medium. Transmission images are collected at the wavelength of maximum dye absorption (630 nm). Where the cell body displaces the dye, the thickness of the absorbing layer is reduced; thus, an increase in cell thickness produces brighter images and vice versa. The absolute values for cell thickness and volume can be easily extracted from the image by computing the logarithm of intensity and dividing it by the absorption coefficient. The method is fast, impervious to instability of the light source, and has a high signal-to-noise ratio; it can be realized either on a laser scanning or a conventional microscope equipped with a bandpass filter. For long-term experiments, we use a Bioptechs perfusion chamber fitted with a 0.03-mm spacer and an additional port to enable rapid switching of solutions. To show possible applications of this method, we investigated the kinetics of the cell volume response to a hypotonic buffer and to the apoptotic agents staurosporine and ionomycin.

Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection.

BACKGROUND: The prostate gland represents a multifaceted system in which prostate epithelia and stroma have distinct physiological roles. To understand the interaction between stroma and glandular epithelia, it is essential to delineate the gene expression profiles of these two tissue types in prostate cancer. Most studies have compared tumor and normal samples by performing global expression analysis using a mixture of cell populations. This report presents the first study of prostate tumor tissue that examines patterns of differential expression between specific cell types using laser capture microdissection (LCM). METHODS: LCM was used to isolate distinct cell-type populations and identify their gene expression differences using oligonucleotide microarrays. Ten differentially expressed genes were then analyzed in paired tumor and non-neoplastic prostate tissues by quantitative real-time PCR. Expression patterns of the transcription factors, WT1 and EGR1, were further compared in established prostate cell lines. WT1 protein expression was also examined in prostate tissue microarrays using immunohistochemistry. RESULTS: The two-step method of laser capture and microarray analysis identified nearly 500 genes whose expression levels were significantly different in prostate epithelial versus stromal tissues. Several genes expressed in epithelial cells (WT1, GATA2, and FGFR-3) were more highly expressed in neoplastic than in non-neoplastic tissues; conversely several genes expressed in stromal cells (CCL5, CXCL13, IGF-1, FGF-2, and IGFBP3) were more highly expressed in non-neoplastic than in neoplastic tissues. Notably, EGR1 was also differentially expressed between epithelial and stromal tissues. Expression of WT1 and EGR1 in cell lines was consistent with these patterns of differential expression. Importantly, WT1 protein expression was demonstrated in tumor tissues and was absent in normal and benign tissues. CONCLUSIONS: The prostate represents a complex mix of cell types and there is a need to analyze distinct cell populations to better understand their potential interactions. In the present study, LCM and microarray analysis were used to identify novel gene expression patterns in prostate cell populations, including identification of WT1 expression in epithelial cells. The relevance of WT1 expression in prostate cancer was confirmed by analysis of tumor tissue and cell lines, suggesting a potential role for WT1 in prostate tumorigenesis.

Undressing "health fashion": an examination of health-cause clothing and accessories.

Today, fashion items such as rubber wristbands in various colors, pink ribbons, and red dresses represent different health-related causes and can be seen frequently across demographic groups. Complete with pithy slogans (e.g., "Go Red for Women"), these items are part of a larger "health fashion" trend--one that involves wearing, using, and displaying health-cause clothing and accessories. In this article, the authors explore recent interest in "health fashion," examining in particular its origins, effectiveness, and implications.

Development of a telehealth intervention for head and neck cancer patients.

Treatment for head and neck cancer precipitates a myriad of distressing symptoms. Patients may be isolated both physically and socially and may lack the self-efficacy to report problems and participate as partners in their care. The goal of this project was to design a telehealth intervention to address such isolation, develop patient self-efficacy, and improve symptom management during the treatment experience. Participatory action research and a review of the literature were used to develop electronically administered symptom management algorithms addressing all major symptoms experienced by patients undergoing treatment for head and neck cancers. Daily questions and related messages were then programmed into an easy-to-use telehealth messaging device, the Health Buddy(R). Clinician and patient acceptance, feasibility, and technology issues were measured. Using participatory action research is an effective means for developing electronic algorithms acceptable to both clinicians and patients. The use of a simple tele-messaging device as an adjunct to symptom management is feasible, affordable, and acceptable to patients. This telehealth intervention provides support and education to patients undergoing treatment for head and neck cancers.