Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status

INTRODUCTION: To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse. METHODS: The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR. RESULTS: The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse. CONCLUSION: CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs

Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

Background: An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Methods: Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. Results: HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Conclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic value. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies

Sequencing of diverse mandarin, pummelo and orange genomes reveals complex history of admixture during citrus domestication

Cultivated citrus are selections from, or hybrids of, wild progenitor species whose identities and contributions to citrus domestication remain controversial. Here we sequence and compare citrus genomes-a high-quality reference haploid clementine genome and mandarin, pummelo, sweet-orange and sour-orange genomes-and show that cultivated types derive from two progenitor species. Although cultivated pummelos represent selections from one progenitor species, Citrus maxima, cultivated mandarins are introgressions of C. maxima into the ancestral mandarin species Citrus reticulata. The most widely cultivated citrus, sweet orange, is the offspring of previously admixed individuals, but sour orange is an F1 hybrid of pure C. maxima and C. reticulata parents, thus implying that wild mandarins were part of the early breeding germplasm. A Chinese wild 'mandarin' diverges substantially from C. reticulata, thus suggesting the possibility of other unrecognized wild citrus species. Understanding citrus phylogeny through genome analysis clarifies taxonomic relationships and facilitates sequence-directed genetic improvement. (Résumé d'auteur

HEALTHY AND OBESE CLASSIFICATIONS: INFLUENCE ON CONSTANT LOAD TREADMILL BOUTS RESULTS

Mariana V. Jacobs, Trey R. Naylor, Justin Pol, Michael Samaan, Jody L. Clasey, FACSM. University of Kentucky, Lexington, KY. BACKGROUND: It has been previously reported that obese individuals have greater absolute and lower relative oxygen consumption measures compared to their healthy-weight counterparts during constant load exercise. However, the method of determining obesity status may significantly influence the results and conclusions of group comparisons. The purpose of this study was to compare the influence of classification methodology by using body mass index (BMI kg • m-2) and body fat percentage (%Fat) to assess oxygen consumption rates (VO2) during submaximal, constant load exercise. METHODS: Seventeen participants (F:8, Age 23.4 ± 2.7yrs) completed a 30-minute walking task on a treadmill at a constant self-selected speed while wearing a portable metabolic system to measure relative VO2 (mL• kg-1 • min-1). All participants underwent a total body DXA scan to assess %Fat. Participants were categorized as healthy (H) or obese (O) using two methods: 1) %Fat (World Health Organization; WHO) and 2) BMI. WHO guidelines indicate healthy %fat for females and males as 21-32% and 8-19%, respectively, with obese classified as those that exceed these sex specific ranges. A BMI of \u3c30 kg • m-2 and \u3e30 kg • m-2 were used to categorize participants as healthy and obese, respectively. Unpaired t-tests (p\u3c0.05) were used to assess between group differences as a function of categorization (WHO vs. BMI). Dependent variables included: walking speed (m • s-1), VO2 at the start (T0), end (T30), the change of VO2 (ΔVΟ2; T30-T0) and total VO2. RESULTS: When using BMI as classification criteria (H:11, O:6), obese participants had significantly lower VO2 at T0 (p\u3c0.01) and T30 (p=0.01), leading to a significantly lower total VO2 (p=0.01). Additionally, the obese participants walked at a 17.5% slower speed (p=0.04). When classified using the %Fat (H:8, O:9), healthy and obese participants walked at similar speeds (p=0.20) yet the obese group displayed trends of lower VO2 at T0 (p=0.07) and T30 (p=0.07) as well trends of lower total V02 (p=0.07). The ΔVΟ2 was similar between groups regardless of using the %Fat (p=0.44) or BMI (p=0.42) criterion. CONCLUSION: These results concur with previous results that in obese individuals, relative VO2 is lower when compared to healthy weight individuals during constant load exercise, despite criterion used. Future research will explore additional ways to classify participants for group comparative purposes

Projecting Stability to the South: NATO’s “New” Mission?

The article of record as published may be found at https://doi.org/10.1007/978-3-030-23641-0_