254 research outputs found
The significance of HPV in the follow-up period after treatment for CIN
High-risk anogenital human papillomavirus (HPV) infections are causally related to cervical cancer. Successful treatment of cervical intraepithelial neoplasia (CIN) results in complete eradication of HPV in most cases. There is an increasing interest regarding the role of HPV testing in the follow-up period after treatment for CIN
Retinoid X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) expression in breast cancer: an immunohistochemical study
The role of retinoid X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) in breast cancer has been well studied in vitro. The aim of the study was to assess the presence of these molecules in human breast cancer specimens and correlate them with major clinicopathological features
Thyroid Hormone Receptors Predict Prognosis in BRCA1 Associated Breast Cancer in Opposing Ways.
Since BRCA1 associated breast cancers are frequently classified as hormone receptor negative or even triple negative, the application of endocrine therapies is rather limited in these patients. Like hormone receptors that bind to estrogen or progesterone, thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily. TRs might be interesting biomarkers - especially in the absence of classical hormone receptors. The current study aimed to investigate whether TRs may be specifically expressed in BRCA1 associated cancer cases and whether they are of prognostic significance in these patients as compared to sporadic breast cancer cases. This study analyzed TRα and TRβ immunopositivity in BRCA1 associated (n = 38) and sporadic breast cancer (n = 86). Further, TRs were studied in MCF7 (BRCA1 wildtype) and HCC3153 (BRCA1 mutated) cells. TRβ positivity rate was significantly higher in BRCA1 associated as compared to sporadic breast cancers (p = 0.001). The latter observation remained to be significant when cases that had been matched for clinicopathological criteria were compared (p = 0.037). Regarding BRCA1 associated breast cancer cases TRβ positivity turned out to be a positive prognostic factor for five-year (p = 0.007) and overall survival (p = 0.026) while TRα positivity predicted reduced five-year survival (p = 0.030). Activation of TRβ resulted in down-modulation of CTNNB1 while TRα inhibition reduced cell viability in HCC3153. However, only BRCA1 wildtype MCF7 cells were capable of rapidly degrading TRα1 in response to T3 stimulation. Significantly, this study identified TRβ to be up-regulated in BRCA1 associated breast cancer and revealed TRs to be associated with patients' prognosis. TRs were also found to be expressed in triple negative BRCA1 associated breast cancer. Further studies need to be done in order to evaluate whether TRs may become interesting targets of endocrine therapeutic approaches, especially when tumors are triple-negative
Fate of ¹⁵N-depleted fertilizer N in a corn-rye cropping sequence: plant uptake and soil distribution
A field experiment was conducted in the Ridge and Valley region of Virginia near Blacksburg during the 1989 through 1991 corn-rye growing seasons. The treatments in this experiment consisted of varying amounts of ¹⁵N-depleted fertilizer N applied to corn (Zea mays L.) at planting followed by a winter rye (Secale cereale L.) cover crop treatment. The research was divided into four studies. The first study was conducted to evaluate an analytical procedure that could be used for the diffusion of low masses of ¹⁵N-labeled NH₄ in 2M KCI and subsequent analysis for N recovery and ¹⁵N concentrations in soil by direct combustion mass spectrometry. Diffusion was found to be a suitable technique for preparing low-mass N samples for automated ¹⁵N analysis by Automated Nitrogen-Carbon Analysis/Mass Spectrometry (ANCA/MS). Recoveries of low masses of added N were quantitative, and accurate ¹⁵N concentrations were obtained when the results were corrected for isotope dilution due to background or contaminant N.
The second study was conducted to determine if ¹⁵N-depleted fertilizer N could be satisfactorily used as a tracer of residual fertilizer N in plant tissue and various soil N fractions through a corn-winter rye crop rotation. Fertilizer-derived N in the soil NO₃-N fraction following corn harvest was clearly detectable and distinguishable from natural abundance to a 90-cm depth. Detection of fertilizer N in the total N pool below the 30-cm depth was not reliable, particularly at the lower N rates. Clay-fixation of fertilizer N measured at corn harvest was not detected by ¹⁵N analysis. Inconclusive results indicate that further research is needed to determine the feasibility of using depleted material for measuring clay-fixation of fertilizer-derived NH₄⁺-N. Nitrogen uptake by a winter rye cover crop reduced soil NO₃-N levels below that required for accurate isotope-ratio analysis. Following winter fallow (approx. 1 yr after fertilizer application) residual ¹⁵N-depleted fertilizer N was still detectable in plant tissue and the soil NO₃-N fraction.
The objectives of the third study were to measure plant uptake and soil distribution of fertilizer N applied to corn at varying N rates and to determine the relationships between economic optimum N rate, fertilizer-use efficiency, and potential leaching loss of residual fertilizer N to groundwater. Plant recovery of fertilizer N in 1989 ranged from 33 to 47% even though no grain yield and fertilizer N uptake response resulted from N fertilization. Greatest accumulation of residual fertilizer N was found in the surface 30-cm both years following corn harvest. The economic optimum N rate for 1990 corn planted into a rye mulch (218 kg N ha⁻¹) corresponded closely with the rate (224 kg N ha⁻¹) resulting in the highest fertilizer-use efficiency. Low levels of residual fertilizer-derived NO₃ in the 60-90-cm depth following the 1990 corn harvest provides evidence to support the use of the economic optimum N rate concept from both economic and environmental viewpoints.
The fourth study was designed to measure the effectiveness of a winter rye cover crop for recovering residual fertilizer N from the previous application of varying N rates to corn. Recovery of fertilizer N by winter rye increased with increasing N rate applied to the previous corn crop and ranged from 3.5 to 35.9 kg N ha⁻¹ in 1990 and 2.3 to 25.7 kg N ha⁻¹ in 1991. Residual fertilizer N recovery in 1991 was higher in rye plots where the previous corn crop had been planted no-till into rye stubble as compared to corn planted no-till into rye mulch. Little or no fertilizer-derived mineral N was measured in the soil to a final depth of 90-cm following a winter rye cover crop. Amounts of fertilizer-derived mineral N increased with depth and previous fertilizer N rate applied to corn following winter fallow. These results provide evidence to support the use of a winter rye cover crop on a silt loam soil to recover residual fertilizer-derived mineral N that might otherwise be lost to groundwater.Ph. D
Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients
Background
Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients.
Methods
Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score.
Results
TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival.
Conclusions
This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols
HPV vaccination: attitude and knowledge among german gynecologists
Purpose: In order to achieve a higher vaccination rate, education on HPV as well as options for prophylaxis performed by doctors is of great importance. One opportunity to increase the protection against HPV would be vaccinating boys. This study evaluated attitude and knowledge among German gynecologists regarding HPV vaccination, especially in boys. Material and Methods: A questionnaire with 42 questions about demographics, attitude and knowledge about HPV and HPV vaccination was sent to members of the German Society for Gynecology and Obstetrics (DGGG). Results: 998 out of 6567 addressed gynecologists participated. Knowledge about HPV, associated diseases and possible HPV vaccines was high among participants. The attitude towards vaccination in boys as well as girls was positive. Only 8.2 % refused to vaccinate their sons whereas 2.2 % refused to do this for their daughters. However, only few gynecologists vaccinated their daughters and sons against HPV. Main reason for girls was an age outside of vaccination guidelines; for boys it was the lack of cost coverage. Conclusion: The willingness of gynecologists to perform HPV vaccination in boys is as high as for girls. However, sons of gynecologists are only rarely vaccinated against HPV. Main reason is the lack of cost coverage. Vaccinating boys could decrease the disease burden in males, as well as protect women by interrupting ways of transmission. Since the main argument against vaccination of boys is only of financial nature, the necessity of a vaccination recommendation for boys needs to be re-evaluated taking into account the cost-reduced 2-dose vaccination scheme
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