Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>New biomarkers that replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for detection of ovarian cancer in the presurgical setting, as well as for detection of disease recurrence. We previously demonstrated the upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) in the sera of ovarian cancer patients compared to healthy women using quantitative mass spectrometry.</p> <p>Methods</p> <p>LRG1 was quantified by ELISA in serum from two relatively large cohorts of women with ovarian cancer and benign gynecological disease. The expression of LRG1 in ovarian cancer tissues and cell lines was examined by gene microarray, reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry and mass spectrometry.</p> <p>Results</p> <p>Mean serum LRG1 was higher in 58 ovarian cancer patients than in 56 healthy women (89.33 ± 77.90 vs. 42.99 ± 9.88 ug/ml; p = 0.0008) and was highest among stage III/IV patients. In a separate set of 193 pre-surgical samples, LRG1 was higher in patients with serous or clear cell ovarian cancer (145.82 ± 65.99 ug/ml) compared to patients with benign gynecological diseases (82.53 ± 76.67 ug/ml, p < 0.0001). CA125 and LRG1 levels were moderately correlated (r = 0.47, p < 0.0001). <it>LRG1 </it>mRNA levels were higher in ovarian cancer tissues and cell lines compared to their normal counterparts when analyzed by gene microarray and RT-PCR. LRG1 protein was detected in ovarian cancer tissue samples and cell lines by immunocytochemistry and Western blotting. Multiple iosforms of LRG1 were observed by Western blot and were shown to represent different glycosylation states by digestion with glycosidase. LRG1 protein was also detected in the conditioned media of ovarian cancer cell culture by ELISA, Western blotting, and mass spectrometry.</p> <p>Conclusions</p> <p>Serum LRG1 was significantly elevated in women with ovarian cancer compared to healthy women and women with benign gynecological disease, and was only moderately correlated with CA125. Ovarian cancer cells secrete LRG1 and may contribute directly to the elevated levels of LRG1 observed in the serum of ovarian cancer patients. Future studies will determine whether LRG1 may serve as a biomarker for presurgical diagnosis, disease recurrence, and/or as a target for therapy.</p

Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study

Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions.Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets.Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) ( < 0.001), stage ( = 0.009), CA125 ( < 0.001), ascites ( < 0.001), and stage-age interaction ( = 0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI).We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool

Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol

To report clinical and pathologic relationships with disease spread in endometrial cancer patients

The concept of negative pressure wound therapy (NPWT) after poststernotomy mediastinitis – a single center experience with 54 patients

Deep sternal infections, also known as poststernotomy mediastinitis, are a rare but often fatal complication in cardiac surgery. They are a cause of increased morbidity and mortality and have a significant socioeconomic aspect concerning the health system. Negative pressure wound therapy (NPWT) followed by muscular pectoralis plasty is a quite new technique for the treatment of mediastinitis after sternotomy. Although it could be demonstrated that this technique is at least as safe and reliable as other techniques for the therapy of deep sternal infections, complications are not absent. We report about our experiences and complications using this therapy in a set of 54 patients out of 3668 patients undergoing cardiac surgery in our institution between January 2005 and April 2007

Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

<p>Abstract</p> <p>Background</p> <p>One of the important factors of the demineralization and remineralization equilibrium of enamel is the pH of the surrounding solutions. Effort has been laid in the formulation of different fluoride compounds and the fluoride content in toothpastes but much less is known about the influence of the pH of the toothpastes on their effectiveness. It was therefore the aim of this study to investigate the influence of different pH levels on enamel remineralization in an in vitro experiment using polarization light microscopy and EDX quantitative element analysis.</p> <p>Methods</p> <p>A 5 × 5 mm window on the enamel surface of 40 caries free extracted human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 8 groups and the lower half of the window was covered with varnish serving as control. Each group was then immersed in toothpaste slurry containing amine fluoride (1400 ppm) at pH 4.1, 4.5, 5.1 and 6.9 or control toothpaste slurry without fluoride at pH 4.3, 4.7, 5.3 and 7.0. Serial sections were cut through the lesions and investigated with polarization light microscopy and quantitative EDX element analysis.</p> <p>Results</p> <p>The PLM results showed a decreased porous volume of the body of the lesion after incubation with fluoridated toothpaste at pH 4.53 and 5.16. No differences between the experimental window and the control window were found in the other groups. The quantitative element analysis showed no differences in the element content of any of the groups.</p> <p>Conclusion</p> <p>From the results it can be concluded that slightly acidified fluoridated dentifrices may have a certain positive effect on enamel remineralization.</p

Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer

Anti-estrogen therapy appears to have efficacy in a subset of ovarian cancers, as demonstrated in multiple phase II studies. Identifying sensitive patients early in treatment may allow for targeted, low-toxicity primary therapy or prevention of recurrence. We have previously demonstrated that the likelihood of response to letrozole could be improved by patient selection based on estrogen-pathway marker expression. We sought to identify ovarian cancer biomarkers that might indicate sensitivity to fulvestrant, an estrogen receptor antagonist

Biological Insights into Chemotherapy Resistance in Ovarian Cancer

The majority of patients with high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy; however, most will develop chemotherapy resistance. Gene signatures may change with the development of chemotherapy resistance in this population, which is important as it may lead to tailored therapies. The objective of this study was to compare tumor gene expression profiles in patients before and after treatment with neoadjuvant chemotherapy (NACT). Tumor samples were collected from six patients diagnosed with HGSOC before and after administration of NACT. RNA extraction and whole transcriptome sequencing was performed. Differential gene expression, hierarchical clustering, gene set enrichment analysis, and pathway analysis were examined in all of the samples. Tumor samples clustered based on exposure to chemotherapy as opposed to patient source. Pre-NACT samples were enriched for multiple pathways involving cell cycle growth. Post-NACT samples were enriched for drug transport and peroxisome pathways. Molecular subtypes based on the pre-NACT sample (differentiated, mesenchymal, proliferative and immunoreactive) changed in four patients after administration of NACT. Multiple changes in tumor gene expression profiles after exposure to NACT were identified from this pilot study and warrant further attention as they may indicate early changes in the development of chemotherapy resistance