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

The Relationship Between Psychic Distance and Expatriate Adjustment to Host Countries

Multinational corporations send expatriates all around the world to live and work. Expatriates’ adjustment to the host country partially determines their success abroad. A handful of studies have examined the relationship between cultural distance and adjustment; however, the results of these studies have been inconsistent. Some studies suggest that adjustment is greater when the home and host countries are more similar, whereas others suggest that there is no relationship between cultural distance and adjustment at all. It is possible, however, that the relationship between cultural distance and adjustment depends on previous experience or host-national contact. It is also possible that psychic distance, which includes cultural distance and a variety of other factors, predicts adjustment better than cultural distance alone. The main purpose of this study was to determine whether the relationship between psychic distance and adjustment depends on previous experience and contact with host nationals. Eighty-seven American expatriates on assignment in twenty-one countries completed mailed questionnaires assessing previous experience, host-national contact, and adjustment to the foreign culture. Psychic distance was calculated by assessing cultural and geographic distance between the home and host country as well as differences in language, education level, industrial development, political system, and religion. Hypotheses were tested using multiple regression procedures

Osteoclasts: malefactors of disease and targets for treatment.

The osteoclast represents one of the most highly specialized cells within the human body, which operates within a microenvironment of diverse cellular populations and matrix proteins. Moreover, the osteoclast directly effects and is affected by these surroundings in a delicate relationship of cellular differentiation, bone resorption, and controlled apoptosis. The result is the maintenance of adequate bone mass throughout life. Unsurprisingly, disturbances within this environment or the molecular regulation of normal osteoclast biology has profound effects on skeletal homeostasis and crippling physical manifestations. This review will summarize current literature describing normal and pathological osteoclast biology and highlight the benefits of osteoclast-targeted therapy to combat skeletal disorders

Current Challenges for Early Career Researchers in Academic Research Careers: COVID‐19 and Beyond

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170886/1/jbm410540.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170886/2/jbm410540_am.pd

School-life conflict and its relationship to student well-being

The goal of this study is to develop and test a new measure of school-life conflict (SLC) as well as to create a model to better understand the personal characteristics associated with school-life conflict. Schoollife conflict is the extent to which life demands, such as work and family, interfere with students’ ability to function at school. We are interested in the extent to which neuroticism and affective organizational commitment influence the experience of school-life conflict, as well as the extent to which school-life conflict and neuroticism influence students’ evaluations of their physical and mental health. Specifically, we expect that the relationship between affective organizational commitment (i.e., emotional attachment to the organization) and school-life conflict will be moderated by neuroticism, such that when neuroticism is high, high affective organizational commitment will lead to high school-life conflict, whereas low affective organizational commitment will lead to low school-life conflict. When neuroticism is low, school-life conflict will be low regardless of degree of affective organizational commitment. Moreover, we predict that the relationship between school-life conflict and health will be moderated by neuroticism, such that when neuroticism is high, high school-life conflict will lead to lower health, whereas low school-life conflict will lead to higher health. When neuroticism is low, health will be higher regardless of level of school -life conflict. Implications for methods of reducing SWC and enhancing student coping skills and health will be discussed

Electrophysiologic manifestations of ventricular tachyarrhythmias provoking appropriate defibrillator interventions in high-risk patients with hypertrophic cardiomyopathy.

Our objective was to determine features of ventricular tachyarrhythmias triggering appropriate implantable cardioverter-defibrillator (ICD) interventions in hypertrophic cardiomyopathy (HCM)

The immunome of mobilized peripheral blood stem cells is predictive of long-term outcomes and therapy-related myeloid neoplasms in patients with multiple myeloma undergoing autologous stem cell transplant

Abstract Upfront autologous stem cell transplant (ASCT) is the standard of care for newly diagnosed multiple myeloma (MM) patients. However, relapse is ubiquitous and therapy-related myeloid neoplasms (t-MN) post-ASCT are commonly associated with poor outcomes. We hypothesized that the enrichment of abnormal myeloid progenitors and immune effector cells (IEC) in the peripheral blood stem cells (PBSCs) is associated with a higher risk of relapse and/or development of t-MN. We performed a comprehensive myeloid and lymphoid immunophenotyping on PBSCs from 54 patients with MM who underwent ASCT. Median progression-free (PFS), myeloid neoplasm-free (MNFS), and overall survival (OS) from ASCT were 49.6 months (95% CI: 39.5-Not Reached), 59.7 months (95% CI: 55–74), and 75.6 months (95% CI: 62–105), respectively. Abnormal expression of CD7 and HLA-DR on the myeloid progenitor cells was associated with an inferior PFS, MNFS, and OS. Similarly, enrichment of terminally differentiated (CD27/CD28-, CD57/KLRG1+) and exhausted (TIGIT/PD-1+) T-cells, and inhibitory NK-T like (CD159a+/CD56+) T-cells was associated with inferior PFS, MNFS, and OS post-transplant. Our observation of abnormal myeloid and IEC phenotype being present even before ASCT and maintenance therapy suggests an early predisposition to t-MN and inferior outcomes for MM, and has the potential to guide sequencing of future treatment modalities