Proteomic Analysis of Ovarian Cancer Proximal Fluids: Validation of Elevated Peroxiredoxin 1 in Patient Peripheral Circulation

Background: Epithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy in the United States. Unfortunately, a validated protein biomarker-screening test to detect early stage disease from peripheral blood has not yet been developed. The present investigation assesses the ability to identify tumor relevant proteins from ovarian cancer proximal fluids, including tissue interstitial fluid (TIF) and corresponding ascites, from patients with papillary serous EOC and translates these findings to targeted blood-based immunoassays. Methodology/Principal Findings: Paired TIF and ascites collected from four papillary serous EOC patients at the time of surgery underwent immunodepletion, resolution by 1D gel electrophoresis and in-gel digestion for analysis by liquid chromatography-tandem mass spectrometry, which resulted in an aggregate identification of 569 and 171 proteins from TIF and ascites, respectively. Of these, peroxiredoxin I (PRDX1) was selected for validation in serum by ELISA and demonstrated to be present and significantly elevated (p = 0.0188) in 20 EOC patients with a mean level of 26.0 ng/mL (±9.27 SEM) as compared to 4.19 ng/mL (±2.58 SEM) from 16 patients with normal/benign ovarian pathology. Conclusions/Significance: We have utilized a workflow for harvesting EOC-relevant proximal biofluids, including TIF and ascites, for proteomic analysis. Among the differentially abundant proteins identified from these proximal fluids, PRDX1 was demonstrated to be present in serum and shown by ELISA to be elevated by nearly 6-fold in papillary serous EOC patients relative to normal/benign patients. Our findings demonstrate the facile ability to discover potential EOC-relevant proteins in proximal fluids and confirm their presence in peripheral blood serum. In addition, our finding of elevated levels of PRDX1 in the serum of EOC patients versus normal/benign patients warrants further evaluation as a tumor specific biomarker for EOC. © 2011 Hoskins et al

A Mixed-Method Multiple Case Study of Three Business Models for Local Healthy Food Delivery Systems in Underprivileged Urban Areas

Define a USDA food desert Analyze the three business models for benefits and deficiencies Identify methods for starting a sustainable mobile farmers market program. Over 40% of Berrien County Michigan land use is agricultural. Many products are fruits and vegetables. Yet, the county has six identified USDA defined Food Deserts. Past research, based on a mobile farmers market, confirmed local trends and deficits. The purpose for this research is to define a sustainable business model that delivers healthy local food options to USDA Food Deserts combating food inequity. A mixed method multiple case study was created to test three business models in one of the local Food Deserts. Results identify a sustainable model that provides local healthy food options. Model One developed lunchtime stops serving robust local businesses and community epicenters, with a goal of creating lunchtime profit, focusing evenings on service stops at a potential loss. Model Two required local farmers to provide produce at no cost to the market. Market locations were service stops embedded inside the residential community and stops increased to 15 per week. Model Three purchased local produce and focused stops on work and shopping locals, targeting the ALICE poverty segment. Models were tested for two weeks each with data collected for correlational comparison. Results show a high demand for lunch hour food options. Labor at such stops was increased over service stops. Model Two proved willingness from local farmers to support neighboring Food Deserts, yet sales didn’t equal market costs. Model Three demonstrated increased demand from ALICE segments. Conclusions indicate that sustainability could be reached with a hybrid model with limited volunteer intern positions. A three to five-year plan should be built with funding support ebbing with market growth

Uterine mullerian adenosarcoma with sarcomatous overgrowth fatal recurrence within two weeks of diagnosis: a case report

Mullerian adenosarcoma with sarcomatous overgrowth (MASO) is a rare variant of uterine sarcomas, associated with postoperative recurrence, metastases and a fatal outcome. The mean age at diagnosis is 54.5 years. A 37-year-old nullipara presented with irregular vaginal bleeding, a normal pelvic examination, and an initially negative ultrasound. Repeat ultrasound one month later revealed an 11-cm heterogeneous pelvic mass. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathology confirmed uterine MASO. Computed tomography 2 weeks postoperatively showed a huge mass compatible with recurrence. Patient died 2 weeks later. MASO is rarely diagnosed in women in their 4th decade. This case stresses that these aggressive tumors should be considered in the differential of patients with vaginal bleeding and pelvic masses irrespective of their age

Demography of an invading forest insect reunited with hosts and parasitoids from its native range

SUPPLEMENTARY MATERIALS : Explanation note: This file includes demographic data from native Sirex nigricornis woodwasps that were collected during our study. TABLE S1. Correlation matrix of bolt-level variables for P. resinosa and P. sylvestris. TABLE S2. Review of 10th and 90th percentile female body mass from insect species estimated from source paper cited, showing comparatively higher female S. noctilio body size variation. FIGURE S1. Examples of S. noctilio oviposition sites, lesion formation and emergence holes in the field. FIGURE S2. Top panels show a typical bolt from P. sylvestris with bark removed and S. noctilio emergence holes and oviposition sites identified. FIGURE S3. The number of S. noctilio emerging per tree was best described by a zero inflated negative binomial distribution (dotted line) with proportion of excess zeroes Φ = 0.32, μ = 75.39 and overdispersion parameter k = 0.35. FIGURE S4. Allometric relationships for S. noctilio in the Central NY data set: number of eggs and adult female mass (a; quantile regression), adult female mass and adult female length (b; fitted power function) and adult length and width of adult head capsule (c; linear regression).The Sirex woodwasp Sirex noctilio Fabricius (Hymenoptera: Siricidae), a widespread invasive pest of pines in the Southern Hemisphere, was first detected in North America in 2004. This study assessed the impacts of life history traits, host resistance and species interactions on the demography of S. noctilio in New York, Pennsylvania and Vermont, then compared key metrics to those found in the native range in Galicia, Spain. Many trees naturally attacked by S. noctilio in North America produced no adult woodwasps, with 5 of 38 infested trees (13%) sampled across six sites yielding 64% of emerging insects. Reproductive success was highest in the introduced host scots pine, Pinus sylvestris, but native red pine, Pinus resinosa, produced larger insects. Sirex noctilio required one or sometimes two years to develop and sex ratios were male biased, 1:2.98 ♀:♂. Body size and fecundity were highly variable, but generally lower than observed in non-native populations in the Southern Hemisphere. Hymenopteran parasitoids killed approximately 20% of S. noctilio larvae and 63% of emerging adults were colonized by the parasitic nematode Deladenus siricidicola, although no nematodes entered eggs. Demographic models suggested that S. noctilio in the northeastern USA have a higher potential for population growth than populations in the native range: estimated finite factor of increase, λ, was 4.17–4.52 (depending on tree species colonized), compared to λ = 1.57 in Spain.USDA Forest Service International Programs and OP RDE.https://neobiota.pensoft.netam2023Forestry and Agricultural Biotechnology Institute (FABI)Zoology and Entomolog

Evaluation of a chemoresponse assay as a predictive marker in the treatment of recurrent ovarian cancer: Further analysis of a prospective study

BACKGROUND: Recently, a prospective study reported improved clinical outcomes for recurrent ovarian cancer patients treated with chemotherapies indicated to be sensitive by a chemoresponse assay, compared with those patients treated with non-sensitive therapies, thereby demonstrating the assay's prognostic properties. Due to cross-drug response over different treatments and possible association of in vitro chemosensitivity of a tumour with its inherent biology, further analysis is required to ascertain whether the assay performs as a predictive marker as well. METHODS: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results. Each patient's tumour was assayed for responsiveness to the 15 therapies. The assay's ability to predict progression-free survival (PFS) was assessed by comparing the association when the assayed therapy matches the administered therapy (match) with the association when the assayed therapy is randomly selected, not necessarily matching the administered therapy (mismatch). RESULTS: Patients treated with assay-sensitive therapies had improved PFS vs patients treated with non-sensitive therapies, with the assay result for match significantly associated with PFS (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.50–0.91, P=0.009). On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66–0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch. While 47% of tumours were non-sensitive to all assayed therapies and 9% were sensitive to all, 44% displayed heterogeneity in assay results. Improved outcome was associated with the administration of an assay-sensitive therapy, regardless of homogeneous or heterogeneous assay responses across all of the assayed therapies. CONCLUSIONS: These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives

Increasing experience in laparoscopic staging of early ovarian cancer

We assessed the effect of increasing experience of a single surgeon (learning curve) in the laparoscopic staging procedure for women with early ovarian cancer and compared the results with the literature. We retrospectively analysed a total of 25 women with apparent early-stage ovarian cancer who underwent a laparoscopic staging procedure by the same surgeon. Three time periods, based on date of surgery, were compared with respect to operating time, amount of lymph nodes harvested and surgical outcome. There was no significant difference in operation time, estimated blood loss and hospital stay between the three periods. There was, however, a significant increase in the median number of pelvic and para-aortal lymph nodes harvested (group1 = 6.5, group 2 = 8.0 and group 3 = 21.0; P < 0.005). For the total period, median operation time was 235 min and median estimated blood loss was 100 ml. The median length of hospital stay was 4.0 days. Two intraoperative and two postoperative complications occurred. The upstaging rate was 32%. The mean interval between initial surgery and laparoscopic staging was 51.2 days. Mean duration of follow-up was 43 months, range (1–116 months). Five (20%) patients had recurrences, and two (8%) patients died of the disease. In conclusion, there is a significant learning curve for the laparoscopic full staging procedure in ovarian cancer. In our study this is mainly reflected in the amount of lymph nodes harvested and not in the total operating time

Intraoperative radiotherapy electron boost in advanced and recurrent epithelial ovarian carcinoma: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis and are almost always fatal. The aim of this study was to evaluate the clinical outcome and toxicity of intraoperative electron beam radiation therapy (IOERT) in advanced and recurrent EOC.</p> <p>Methods</p> <p>Forty-five women with EOC were treated with IOERT. Twenty-five patients had primary disease (PD) without distant metastasis at IOERT, and 20 patients had an isolated local recurrence (ILR) after surgery. All 45 patients in this series underwent optimal cytoreductive (≤ 1 cm) surgery. The whole pelvic (WP) radiotherapy was intraoperatively delivered using 12 Mev electron beam; 43 patients received 18-20 Gy and two patients received 10 Gy. Thirty-three patients received postoperateive intraperitoneal (IP) chemotherapy, while seven patients received intravenous (IV) chemotherapy. Five patients refused concurrent chemotherapy. Overall survival (OS) rates were analyzed using the Kaplan-Meier method.</p> <p>Results</p> <p>Tumor recurrence and metastasis were observed in 16 patients (35.6%). Of those, 14 patients (31.1%) relapsed and two patients (4.4%) had distant metastasis alone. Eight of 25 (32%) local failures were observed in the PD group, as compared to 6/20 (30%) in the ILR group (<it>P </it>= 0.885). Actuarial local control at five year follow-up was 31/45 (68.9%). Seventeen of the total 45 (37.8%) patients died. Nine of 25 (36%) in the PD group died, as compared to 8 of 20 (40%) in the ILR group. The 5-year OS and disease-free survival (DFS) rates were 28/45 (62.2%) and 25/45 (55.6%), respectively. In the PD group, the 5-year OS and DFS rates were 16/25 (64%) and 14/25 (56%) (<it>P </it>> 0.05, <it>vs</it>. the ILR group at 12/20 and 11/20, respectively). The OS and DFS in the IOERT plus IP group were 25/33 (75.8%) and 23/33 (69.7%), respectively, which were superior to the rates achieved with IOERT plus IV chemotherapy (<it>P </it>< 0.05, 2/7 and 1/7, respectively). The major complication of IOERT was neuropathy. Five (11.1%) patients developed peripheral neurotoxicity.</p> <p>Conclusions</p> <p>IOERT may be feasible and effective as a boosting technique for advanced and recurrent ovarian cancer. IOERT plus IP chemotherapy may achieve high locoregional disease control and survival benefit with a low risk of toxicity. Peripheral nerves in the IOERT field are dose-limiting structures requiring nerve protection policies or a dose compromise to ensure against severe neurological damage.</p

Differential Analysis of Ovarian and Endometrial Cancers Identifies a Methylator Phenotype

Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer

PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive