Retinoic Acid-Binding Protein in Human Breast Cancer and Dysplasia

Seventy-five specimens of human breast tissue were checked for the presence of cellular retinoic acid-binding protein (cRABP). Fifty-two percent of the primary carcinomas and 43% of the dysplastic breast lesions (stage MIl) contained detectable amounts of cRABP, whereas no cRABP was found in normal tissue. Sucrose gradient centrifugation and electrophoresis on agarose were used for analysis of the presence of cRABP. The cRABP of human origin (normal uterus and neoplastic mammary tissue) differed in its mobility in agarose electrophoresis from that of rat testis cRA

Long-term outcomes of breast cancer patients after endoscopic axillary lymph node dissection: a prospective analysis of 52 patients

Summary: Background. Reports on long-term outcomes after endoscopic axillary lymph node dissection (ALND) of breast cancer patients are still lacking in the medical literature. The objective of this prospective study was to assess the oncological and functional outcomes in breast cancer patients after endoscopic ALND. Methods. Fifty-five breast cancer patients were prospectively enrolled, of whom 52 were available for follow-up with a median of 71.9 months (range 11-96). The following oncological and functional endpoints were evaluated during follow-up at several time points: occurrence of local, axillary and distant metastases, seroma or infection, shoulder mobility (range of motion), numbness, pain, presence of lymphoedema as well as restriction in activities of daily living. Results. In 52 patients endoscopic ALND of level I and II was successfully performed. Two port-site metastases (2/52, 4%) occurred, one of which in a patient with negative axillary lymph nodes. The same patient suffered from the only axillary recurrence (1/52, 2%). Three patients (3/52, 6%) developed lymphoedema. No other functional adverse events (shoulder mobility, pain, numbness, hypertrophic scar) were noticed at the end of the observation period. Conclusion. The present investigation with long-term follow-up after endoscopic ALND - the first one in the literature - reveals minor morbidity, good functional and cosmetic results. In contrary to conventional surgery, the endoscopic procedure is associated with the occurrence of port-site metastases, not seen in the open approach. Axillary recurrences do not appear more frequently when compared with results after conventional ALND. In the meantime the less invasive sentinel lymph node (SLN) biopsy is the established standard technique in evaluating the axillary lymph node statu

The Effect of Using a Meal Tracking Smartphone Application in Overweight and Obese Adolescents with Prediabetes or Type 2 Diabetes to Improve BMI and HbA1c

Obesity has become one of the most common chronic pediatric illnesses worldwide and is closely linked to the onset of prediabetes and subsequent Type 2 Diabetes (T2D); therefore, preventing and treating childhood obesity has become a high priority (Hampl et al., 2023). The purpose of this Evidence-Based Practice (EBP) project is to lower Glycosylated Hemoglobin A1c (HbA1C) and Body Mass Index (BMI) in overweight and obese youth with prediabetes and T2D using a meal tracking smartphone application. The Johns Hopkins Nursing Evidence-Based Practice Model (JHNEBP) was utilized to pilot this project between two pediatric endocrinology offices located in Southeast Wisconsin. Upon organizational approval of this EBP project, adolescents, aged 10 to 18, were recruited based on strict inclusion criteria including a diagnosis of prediabetes or T2D, obesity defined using the Centers for Disease Control and Prevention’s (CDC) (2022c) BMI percentile calculator specific to children and prior nonuse of a meal tracking smartphone application. A total of 10 adolescents were recruited in 10–15-minute educational encounters. To achieve a reduction in both BMI and HbA1c in these participants, a smartphone application for meal tracking called Nourishly© was utilized to track dietary intake and provide individualized, diet specific education and feedback over a 12-week period. Seven educational handouts were also provided and utilized to help guide app usage as well as provide diabetes specific, dietary education to participants and their families. A paired t test was utilized to analyze the primary outcomes of the project including pre- and post- intervention BMI and HbA1c measures. Results for BMI showed no statistical evidence of a decrease (t =- 0.655(9), p=0.264). Similar results were seen for HbA1c and there was no statistical evidence of a decrease (V=39, p=0.890). This EBP project highlights the need for further research to assess the use of dietary specific smartphone applications and their impact on HbA1c and BMI in overweight and obese youth with prediabetes and T2D in light of the digital era

Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Background: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. Methods: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). Results: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. Conclusions: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therap

Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis

Background: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. Methods: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. Results: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P = .0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P = .0001). Conclusions: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplificatio

Xenosurveillance of Wild Pigs Using Mosquito Bloodmeals

Feral swine are an abundant invasive species that are heavily managed in the United States. We used DNA extracted from the bloodmeals of mosquitos to detect free ranging feral swine in south central Florida. DNA was of a sufficient quantity and quality that downstream applications such as genotyping or Sangar sequencing were feasible. Preliminary analyses were able to detect feral swine in blood-fed mosquitos

Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores

BACKGROUND: Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection. METHODS: In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR. RESULTS: Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan(R) Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient. CONCLUSION: We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen

Prognostic Significance of High Expression of ER-beta in Surgically Treated ER-Positive Breast Cancer Following Endocrine Therapy

Purpose: This study evaluated estrogen receptor (ER)-beta mRNA and ER-beta protein expression and its prognostic implications in hormone receptor-positive breast cancer. Methods: Paraffin sections from 139 hormone receptor-positive breast cancer cases were prepared. The expression of ER-beta mRNA and protein were analyzed by branched-chain assay and immunohistochemistry (IHC), respectively. Results: The Allred score of ER-beta IHC was correlated with smaller tumor size (p=0.043), the Allred score of ER-alpha IHC (p<0.001), and the Allred score of progesterone receptor (PR) IHC (p=0.022) but not with the HER2 IHC score. ER-beta mRNA level was correlated with PR mRNA levels (p<0.001) but not with the Allred score of ER-beta IHC, ER-alpha IHC, and PR IHC, nor with the HER2 IHC score and ER-alpha mRNA level. In survival analysis, high expression of ER-beta mRNA was associated with worse disease-free survival along with poor differentiation, lymph node metastasis and absence of PR protein expression in univariate analysis (p = 0.040, p = 0.002, p = 0.018, and p = 0.007, respectively) and multivariate analysis (p = 0.044, p = 0.002, p = 0.035, and p = 0.007, respectively). Conclusion: High expression of ER-beta mRNA is an independent predictor of disease recurrence in hormone-receptorpositive breast cancer

CONSUMO RESPONSÁVEL DE PESCADO: DE ONDE VEM MEU PEIXE?

OBJECTIVES: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. SEARCH STRATEGY: Electronic databases screened: MEDLINE (from 1966-February 1999); PsycLit (from 1974-March 1999); Embase (from 1980-January 1999); The Cochrane Controlled Trials Register (CCTR) No.1 1999. Ten journals in the field of psychiatry and psychology were hand searched for the first version of this review. We have updated the hand search of three specialist journals in the field of suicidal research until the end of 1998. Reference lists of papers were checked and trialists contacted. SELECTION CRITERIA: All RCTs of psychosocial and/or psychopharmacological treatment versus standard or less intensive types of aftercare for patients who shortly before entering a study engaged in any type of deliberately initiated self-poisoning or self-injury, both of which are generally subsumed under the term deliberate self-harm. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. Studies were categorized according to type of treatment. The outcome measure used to assess the efficacy of treatment interventions for deliberate self-harm was the rate of repeated suicidal behaviour. We have been unable to examine other outcome measures as originally planned (e.g. compliance with treatment, depression, hopelessness, suicidal ideation/thoughts, change in problems/problem resolution). MAIN RESULTS: A total of 23 trials were identified in which repetition of deliberate self-harm was reported as an outcome variable. The trials were classified into 11 categories. The summary odds ratio indicated a trend towards reduced repetition of deliberate self-harm for problem-solving therapy compared with standard aftercare (0.70; 0.45 to 1.11) and for provision of an emergency contact card in addition to standard care compared with standard aftercare alone (0.45; 0.19 to 1.07). The summary odds ratio for trials of intensive aftercare plus outreach compared with standard aftercare was 0.83 (0.61 to 1.14), and for antidepressant treatment compared with placebo was 0.83 (0. 47 to 1.48). The remainder of the comparisons were in single small trials. Significantly reduced rates of further self-harm were observed for depot flupenthixol vs. placebo in multiple repeaters (0. 09; 0.02 to 0.50), and for dialectical behaviour therapy vs. standard aftercare (0.24; 0.06 to 0.93). REVIEWER'S CONCLUSIONS: There still remains considerable uncertainty about which forms of psychosocial and physical treatments of self-harm patients are most effective, inclusion of insufficient numbers of patients in trials being the main limiting factor. There is a need for larger trials of treatments associated with trends towards reduced rates of repetition of deliberate self-harm. The results of small single trials which have been associated with statistically significant reductions in repetition must be interpreted with caution and it is desirable that such trials are also replicated