Thyroid Nodules on Ultrasound in Children and Young Adults: Comparison of Diagnostic Performance of Radiologists' Impressions, ACR TI-RADS, and a Deep Learning Algorithm.

BACKGROUND. In current clinical practice, thyroid nodules in children are generally evaluated on the basis of radiologists' overall impressions of ultrasound images. OBJECTIVE. The purpose of this article is to compare the diagnostic performance of radiologists' overall impression, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), and a deep learning algorithm in differentiating benign and malignant thyroid nodules on ultrasound in children and young adults. METHODS. This retrospective study included 139 patients (median age 17.5 years; 119 female patients, 20 male patients) evaluated from January 1, 2004, to September 18, 2020, who were 21 years old and younger with a thyroid nodule on ultrasound with definitive pathologic results from fine-needle aspiration and/or surgical excision to serve as the reference standard. A single nodule per patient was selected, and one transverse and one longitudinal image each of the nodules were extracted for further evaluation. Three radiologists independently characterized nodules on the basis of their overall impression (benign vs malignant) and ACR TI-RADS. A previously developed deep learning algorithm determined for each nodule a likelihood of malignancy, which was used to derive a risk level. Sensitivities and specificities for malignancy were calculated. Agreement was assessed using Cohen kappa coefficients. RESULTS. For radiologists' overall impression, sensitivity ranged from 32.1% to 75.0% (mean, 58.3%; 95% CI, 49.2-67.3%), and specificity ranged from 63.8% to 93.9% (mean, 79.9%; 95% CI, 73.8-85.7%). For ACR TI-RADS, sensitivity ranged from 82.1% to 87.5% (mean, 85.1%; 95% CI, 77.3-92.1%), and specificity ranged from 47.0% to 54.2% (mean, 50.6%; 95% CI, 41.4-59.8%). The deep learning algorithm had a sensitivity of 87.5% (95% CI, 78.3-95.5%) and specificity of 36.1% (95% CI, 25.6-46.8%). Interobserver agreement among pairwise combinations of readers, expressed as kappa, for overall impression was 0.227-0.472 and for ACR TI-RADS was 0.597-0.643. CONCLUSION. Both ACR TI-RADS and the deep learning algorithm had higher sensitivity albeit lower specificity compared with overall impressions. The deep learning algorithm had similar sensitivity but lower specificity than ACR TI-RADS. Interobserver agreement was higher for ACR TI-RADS than for overall impressions. CLINICAL IMPACT. ACR TI-RADS and the deep learning algorithm may serve as potential alternative strategies for guiding decisions to perform fine-needle aspiration of thyroid nodules in children.

Pediatric Endocrinology Milestones 2.0-guide to their implementation.

The Milestones were initiated by the Accreditation Council for Graduate Medical Education (ACGME) to provide a framework for monitoring a trainee's progression throughout residency/fellowship. The Milestones describe stepwise skill progression through six core domains of clinical competency: Patient Care, Medical Knowledge, Interpersonal and Communication Skills, Practice-based Learning and Improvement, Professionalism, and Systems-based Practice. Since their introduction in 2013, several barriers to implementation have emerged. Thus, the ACGME launched the Milestones 2.0 project to develop updated specialty-specific milestones. The Pediatric Endocrinology Milestones 2.0 project aimed to improve upon Milestones 1.0 by addressing common limitations, providing resources for faculty to easily incorporate milestones into their assessment of trainees, and adding sub-competencies in health disparities, patient safety, and physician well-being.This paper reviews the development of the Pediatric Endocrinology Milestones 2.0 including the major changes from Milestones 1.0, development of the Supplemental Guide, and how Milestones 2.0 can be applied at the program level. Although use of the Milestones are required only for ACGME programs, the tools provided in Milestones 2.0 are applicable to fellowship programs worldwide.

Reduction of volatile fatty acids and odor offensiveness by anaerobic digestion and solid separation of dairy manure during manure storage.

Volatile fatty acids (VFA) play an important role in the biodegradation of organic wastes and production of bioenergy under anaerobic digestion, and are related to malodors. However, little is known about the dynamics of VFA during dairy manure storage. This study evaluated the characteristics of VFA in dairy manure before and after anaerobic co-digestion in a laboratory experiment using eight lab-scale reactors. The reactors were loaded with four different types of dairy manure: (1) liquid dairy manure from a freestall barn, (2) mixture of dairy manure and co-digestion food processing wastes at the inlet of an anaerobic digester, (3) effluent from the digester outlet, and (4) the liquid fraction of effluent from a solid separator. Four VFA (acetic, propionic, butyric, and 2-methylbutyric acids) were identified and quantified in weekly manure samples from all reactors. Results showed that the dominant VFA was acetic acid in all four manure sources. The off-farm co-digestion wastes significantly increased the total VFA concentrations and the proportions of individual VFA in the influent. The dairy manure under storage demonstrated high temporal and spatial variations in pH and VFA concentrations. Anaerobic digestion reduced the total VFA by 86%-96%; but solid-liquid separation did not demonstrate a significant reduction in total VFA in this study. Using VFA as an indicator, anaerobic digestion exhibited an effective reduction of dairy manure odor offensiveness.

Development of a Tool to Measure Student Perceptions of Equity and Inclusion in Medical Schools.

Importance: Creating an inclusive and equitable learning environment is a national priority. Nevertheless, data reflecting medical students' perception of the climate of equity and inclusion are limited. Objective: To develop and validate an instrument to measure students' perceptions of the climate of equity and inclusion in medical school using data collected annually by the Association of American Medical Colleges (AAMC). Design, Setting, and Participants: The Promoting Diversity, Group Inclusion, and Equity tool was developed in 3 stages. A Delphi panel of 9 members identified survey items from preexisting AAMC data sources. Exploratory and confirmatory factor analysis was performed on student responses to AAMC surveys to construct the tool, which underwent rigorous psychometric validation. Participants were undergraduate medical students at Liaison Committee on Medical Education-accredited medical schools in the US who completed the 2015 to 2019 AAMC Year 2 Questionnaire (Y2Q), the administrations of 2016 to 2020 AAMC Graduation Questionnaire (GQ), or both. Data were analyzed from August 2020 to November 2023. Exposures: Student race and ethnicity, sex, sexual orientation, and socioeconomic status. Main Outcomes and Measures: Development and psychometric validation of the tool, including construct validity, internal consistency, and criterion validity. Results: Delphi panel members identified 146 survey items from the Y2Q and GQ reflecting students' perception of the climate of equity and inclusion, and responses to these survey items were obtained from 54 906 students for the Y2Q cohort (median [IQR] age, 24 [23-26] years; 29 208 [52.75%] were female, 11 389 [20.57%] were Asian, 4089 [7.39%] were multiracial, and 33 373 [60.28%] were White) and 61 998 for the GQ cohort (median [IQR] age, 27 [26-28] years; 30 793 [49.67%] were female, 13 049 [21.05%] were Asian, 4136 [6.67%] were multiracial, and 38 215 [61.64%] were White). Exploratory and confirmatory factor analyses of student responses identified 8 factors for the Y2Q model (faculty role modeling; student empowerment; student fellowship; cultural humility; faculty support for students; fostering a collaborative and safe environment; discrimination: race, ethnicity, and gender; and discrimination: sexual orientation) and 5 factors for the GQ model (faculty role modeling; student empowerment; faculty support for students; discrimination: race, ethnicity, and gender; and discrimination: sexual orientation). Confirmatory factor analysis indicated acceptable model fit (root mean square error of approximation of 0.05 [Y2Q] and 0.06 [GQ] and comparative fit indices of 0.95 [Y2Q] and 0.94 [GQ]). Cronbach α for individual factors demonstrated internal consistency ranging from 0.69 to 0.92 (Y2Q) and 0.76 to 0.95 (GQ). Conclusions and Relevance: This study found that the new tool is a reliable and psychometrically valid measure of medical students' perceptions of equity and inclusion in the learning environment.

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant.

The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat mass during mid- and late gestation and the early postnatal period in the context of changes in the secretion and action of maternal, placental, fetal, and neonatal hormones, growth factors, and adipocytokines. We assess the effects of hormonal determinants on placental nutrient delivery and the impact of preterm delivery on hormone expression and postnatal growth and metabolic function. We then discuss the effects of various maternal disorders and nutritional and pharmacologic interventions on fetal and perinatal hormone and growth factor production, growth, and fat deposition and consider important unresolved questions in the field.

Successful Management of Cushing Syndrome From Ectopic ACTH Secretion in an Adolescent With Osilodrostat.

A previously healthy 11-year-old male was found to have a mass in the pancreatic head after several months of abdominal pain and jaundice. Pathology was consistent with a World Health Organization grade 2 pancreatic neuroendocrine tumor. He developed refractory hypertension and was found to have Cushing syndrome from ectopic ACTH secretion, with oligometastatic liver disease. He underwent surgical resection of the pancreatic tumor and metastases. Postoperatively, his Cushing syndrome resolved, but it reemerged 1 year later in the setting of disease recurrence. He was not a candidate for bilateral adrenalectomy. Ketoconazole therapy was inadequate and he was started on metyrapone, lanreotide, cabergoline, and spironolactone. Although this regimen was well-tolerated, his Cushing syndrome recurred 4 months later as his metastatic disease burden increased. Osilodrostat was begun and the dose was gradually increased in response to his uncontrolled Cushing syndrome. Osilodrostat resulted in rapid improvement and eventual normalization of his urinary free cortisol at a dose of 18 mg twice daily. He had no adverse effects. This rare case highlights the successful off-label use of osilodrostat, a medication intended for refractory Cushing disease in adult patients, in a pediatric patient with Cushing syndrome caused by ectopic ACTH secretion.

Perspectives on National Institutes of Health Funding Requirements for Racial and Ethnic Diversity Among Medical Scientist Training Program Leadership.

Importance: Since 1964, the National Institutes of Health (NIH) has funded the Medical Scientist Training Program (MSTP) MD-PhD program at medical schools across the US to support training physician-scientists. Recent studies have suggested that MSTPs have consistently matriculated more students from racial and ethnic backgrounds historically underrepresented in science than MD-PhD programs without NIH funding; however, the underlying basis for the increased diversity seen in NIH-funded MSTPs is poorly understood. Objective: To investigate how administrators and faculty perceive the impact of MSTP status on MD-PhD program matriculant racial and ethnic diversity. Design, Setting, and Participants: This qualitative study used a positive deviance approach to identify 9 high-performing and 3 low-performing MSTPs based on the percentage of students underrepresented in science who matriculated into the program between 2014 and 2018. This study, a subanalysis of a larger study to understand recruitment of students underrepresented in science at MSTPs, focused on in-depth qualitative interviews, conducted from October 26, 2020, to August 31, 2022, of 69 members of MSTP leadership, including program directors, associate and assistant program directors, and program administrators. Main Outcomes and Measures: The association of NIH funding with institutional priorities, programs, and practices related to MD-PhD program matriculant racial and ethnic diversity. Results: The study included 69 participants (mean [SD] age, 53 [10] years; 38 women [55%]; 13 African American or Black participants [19%], 6 Asian participants [9%], 12 Hispanic participants [17%], and 36 non-Hispanic White participants [52%]). A total of 51 participants (74%) were in administrative roles, and 18 (26%) were faculty involved in recruitment. Five themes emerged from the data: (1) by tying MSTP funding to diversity efforts, the NIH created a sense of urgency among MSTP leadership to bolster matriculant diversity; (2) MD-PhD program leadership leveraged the changes to MSTP grant review to secure new institutional investments to promote recruitment of students underrepresented in science; (3) MSTPs increasingly adopted holistic review to evaluate applicants to meet NIH funding requirements; (4) MSTP leadership began to systematically assess the effectiveness of their diversity initiatives and proactively identify opportunities to enhance matriculant diversity; and (5) although all MSTPs were required to respond to NIH criteria, changes made by low-performing programs generally lacked the robustness demonstrated by high-performing programs. Conclusions and Relevance: This study suggests that NIH funding requirements may be a powerful incentive to promote diversity and positively affect representation of students underrepresented in science in the biomedical scientific workforce.

Bladder expression of CD cell surface antigens and cell-type-specific transcriptomes.

Many cell types have no known functional attributes. In the bladder and prostate, basal epithelial and stromal cells appear similar in cytomorphology and share several cell surface markers. Their total gene expression (transcriptome) should provide a clear measure of the extent to which they are alike functionally. Since urologic stromal cells are known to mediate organ-specific tissue formation, these cells in cancers might exhibit aberrant gene expression affecting their function. For transcriptomes, cluster designation (CD) antigens have been identified for cell sorting. The sorted cell populations can be analyzed by DNA microarrays. Various bladder cell types have unique complements of CD molecules. CD9(+) urothelial, CD104(+) basal and CD13(+) stromal cells of the lamina propria were therefore analyzed, as were CD9(+) cancer and CD13(+) cancer-associated stromal cells. The transcriptome datasets were compared by principal components analysis for relatedness between cell types; those with similarity in gene expression indicated similar function. Although bladder and prostate basal cells shared CD markers such as CD104, CD44 and CD49f, they differed in overall gene expression. Basal cells also lacked stem cell gene expression. The bladder luminal and stromal transcriptomes were distinct from their prostate counterparts. In bladder cancer, not only the urothelial but also the stromal cells showed gene expression alteration. The cancer process in both might thus involve defective stromal signaling. These cell-type transcriptomes provide a means to monitor in vitro models in which various CD-isolated cell types can be combined to study bladder differentiation and bladder tumor development based on cell-cell interaction.

Institutional variation in the promotion of racial/ethnic minority faculty at US medical schools.

OBJECTIVES: We compared faculty promotion rates by race/ethnicity across US academic medical centers. METHODS: We used the Association of American Medical College's 1983 through 2000 faculty roster data to estimate median institution-specific promotion rates for assistant professor to associate professor and for associate professor to full professor. In unadjusted analyses, we compared medians for Hispanic and Black with White faculty using the Wilcoxon rank sum test. We compared institution-specific promotion rates between racial/ethnic groups with data stratified by institutional characteristic (institution size, proportion racial/ethnic minority faculty, and proportion women faculty) using the χ(2) test. Our sample included 128 academic medical centers and 88, 432 unique faculty. RESULTS: The median institution-specific promotion rates for White, Hispanic, and Black faculty, respectively, were 30.2%, 23.5%, and 18.8% (P < .01) from assistant to associate professor and 31.5%, 25.0%, and 16.7% (P < .01) from associate to full professor. CONCLUSIONS: At most academic medical centers, promotion rates for Hispanic and Black were lower than those for White faculty. Equitable faculty promotion rates may reflect institutional climates that support the successful development of racial/ethnic minority trainees, ultimately improving healthcare access and quality for all patients.

Pharmacologic Weight Management in the Era of Adolescent Obesity.

CONTEXT: Pediatric obesity is a serious health problem in the United States. While lifestyle modification therapy with dietary changes and increased physical activity are integral for the prevention and treatment of mild to moderate obesity in youth, only a modest effect on sustained weight reduction is observed in children and young adults with severe obesity. This underscores the need for additional evidence-based interventions for children and adolescents with severe obesity, including pharmacotherapy, before considering invasive procedures such as bariatric surgery. EVIDENCE ACQUISITION: This publication focuses on recent advances in pharmacotherapy of obesity with an emphasis on medications approved for common and rarer monogenic forms of pediatric obesity. EVIDENCE SYNTHESIS: We review medications currently available in the United States, both those approved for weight reduction in children and "off-label" medications that have a broad safety margin. CONCLUSION: It is intended that this review will provide guidance for practicing clinicians and will encourage future exploration for successful pharmacotherapy and other interventions for obesity in youth.

Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured prostate stromal fibromuscular cells.

The prostate stromal mesenchyme controls organ-specific development. In cancer, the stromal compartment shows altered gene expression compared to non-cancer. The lineage relationship between cancer-associated stromal cells and normal tissue stromal cells is not known. Nor is the cause underlying the expression difference. Previously, the embryonal carcinoma (EC) cell line, NCCIT, was used by us to study the stromal induction property. In the current study, stromal cells from non-cancer (NP) and cancer (CP) were isolated from tissue specimens and co-cultured with NCCIT cells in a trans-well format to preclude heterotypic cell contact. After 3 days, the stromal cells were analyzed by gene arrays for microRNA (miRNA) and mRNA expression. In co-culture, NCCIT cells were found to alter the miRNA and mRNA expression of NP stromal cells to one like that of CP stromal cells. In contrast, NCCIT had no significant effect on the gene expression of CP stromal cells. We conclude that the gene expression changes in stromal cells can be induced by diffusible factors synthesized by EC cells, and suggest that cancer-associated stromal cells represent a more primitive or less differentiated stromal cell type.

Sustained Impact of a Pediatric Resident-Led Patient Safety Council.

OBJECTIVES: The aim of the study was to evaluate the impact of a resident-led patient safety council. This study measured change in resident perceptions and knowledge of safety issues for 3 years, as well as behavioral choices to participate in patient safety activities during and after residency. METHODS: Pediatric residents formed a resident-led safety council to engage their peers in patient safety activities. Surveys were distributed annually from 2013 to 2015 to measure residents' perception and knowledge surrounding patient safety. The number of patient safety reports submitted by residents was tracked for the same period. In addition, recent graduates were surveyed to assess the influence of the council on postresidency involvement in patient safety. RESULTS: Resident perception of the institutional culture of safety improved and knowledge of basic patient safety concepts increased. The number of resident-submitted safety reports increased from 6.2 to 15.2 reports per month in the 2013 and 2015 academic years, respectively. Surveys of recent graduates suggest that involvement with the safety council during residency fostered future engagement in patient safety. CONCLUSIONS: This resident-led council models successful involvement of trainees in system-based patient safety. Such involvement can help shape the safety culture within a training program and encourages continued participation in patient safety after residency completion.

An endocrine perspective on menstrual suppression for adolescents: achieving good suppression while optimizing bone health.

Suppression of menstruation and/or ovarian function in adolescent girls may be desired for a variety of reasons. Numerous medical options exist. The choice of the appropriate modality for an individual patient depends on several factors based on differences in the efficacy of achieving menstrual suppression as well as in their side effect profiles. Adolescence is also a period of bone mass accrual in girls, and several of these modalities may negatively influence peak bone mass. This review focuses on the efficacy of achieving menstrual suppression and the effect on bone health of the various options through an overview of the current literature and also highlights areas in need of further research.

Role of GLP-1 Receptor Agonists in Pediatric Obesity: Benefits, Risks, and Approaches to Patient Selection.

PURPOSE OF REVIEW: Effective treatments for pediatric obesity are limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as therapeutic agents for obesity in adults and have shown benefits outside of weight loss. Here we explore the evidence for GLP-1R agonist use in pediatric obesity. RECENT FINDINGS: Emerging evidence suggests that GLP-1R agonists have a role in pediatric obesity treatment. A recently published, randomized, placebo-controlled trial found a greater reduction in BMI z-score (- 0.22 SDs) in adolescents receiving liraglutide compared with placebo. As in adults, gastrointestinal adverse effects were commonly seen. GLP-1R agonists appear to perform favorably compared with other approved pharmacological agents for pediatric obesity. However, heterogeneity in weight loss response, cost, side effects, and need for injections may limit their use in many pediatric patients. Rather than broadly applying this therapy if it is approved, we suggest careful patient selection and monitoring by clinicians pending further studies.

Achieving Gender Equity Is Our Responsibility: Leadership Matters.

Across academic medicine, and particularly among faculty and medical school leadership, the status quo is unacceptable when it comes to gender diversity, equity, and inclusion. The Association of American Medical Colleges has launched a bold gender equity initiative, endorsed by its Board of Directors, to implore academic medical institutions to take meaningful and effective actions.Defining what progress should look like to guide these actions is worth deeper exploration. It is not enough to measure the representation of different genders at various levels of leadership within our institutions. Research and experience we share suggests more must be done, especially for women of diverse racial and ethnic backgrounds. What is needed is a fundamental conversation about privilege, intersectionality across different backgrounds, and progress.Institutional leaders have a choice to make. Will we make gender equity a top priority system-wide because we recognize that doing so leads to organizational excellence? Do we understand that establishing a robust, comprehensive definition of gender equity and how it is practiced will result in better outcomes for all? And are we ready and able to prioritize and be accountable for efforts that are measurable, with clear definitions of progress; driven and reinforced by leadership directives; inclusive of all, including men as well as women of diverse backgrounds and orientations; and systemic rather than ad-hoc? Implementing such actions requires initiating difficult conversations, making conscious choices, and modeling best practices from leaders who have successfully made gender equity a priority.

Management and Appropriate Use of Diazoxide in Infants and Children with Hyperinsulinism.

BACKGROUND: The diagnosis of hypoglycemia and the use of diazoxide have risen in the last decade. Diazoxide is the only Food and Drug Agency-approved pharmacologic treatment for neonatal hypoglycemia caused by hyperinsulinism (HI). Recent publications have highlighted that diazoxide has serious adverse effects (AEs) such as pulmonary hypertension (2-3%) and neutropenia (15%). Despite its increasing use, there is little information regarding dosing of diazoxide and/or monitoring for AEs. METHODS: We convened a working group of pediatric endocrinologists who were members of the Drug and Therapeutics Committee of the Pediatric Endocrine Society (PES) to review the available literature. Our committee sent a survey to its PES members regarding the use of diazoxide in their endocrine practices. Our review of the results concluded that there was substantial heterogeneity in usage and monitoring for AEs for diazoxide among pediatric endocrinologists. CONCLUSIONS: Based on our extensive literature review and on the lack of consensus regarding use of diazoxide noted in our PES survey, our group graded the evidence using the framework of the Grading of Recommendations, Assessment, Development and Evaluation Working Group, and has proposed expert consensus practice guidelines for the appropriate use of diazoxide in infants and children with HI. We summarized the information on AEs reported to date and have provided practical ideas for dosing and monitoring for AEs in infants treated with diazoxide.

Vivre sans ma voiture : une intervention pour soutenir les Canadiens-francophones âgés.

The cessation of driving is a difficult transition for the elderly, but it can be facilitated through interventions. The purpose of this study was to explore the satisfaction, usefulness and applicability of the CarFreeMe intervention in the French-Canadian context. A qualitative clinical research device was used on ten older adults aged between 61 and 90 years. The participants had stopped driving within the last twelve months or were planning to stop driving in the near future and did not have cognitive impairments. After the intervention, the participants were generally satisfied and reported on its usefulness and applicability in a French-Canadian context. In addition, they identified the positive impacts related to their social involvement as they re-engaged in or pursued their significant activities. Further research is required to assess the intervention's effects and the practicability of implementing it in Canada.

Temporal expression profiling of the effects of secreted factors from prostate stromal cells on embryonal carcinoma stem cells.

BACKGROUND: There is a growing body of evidence indicating that epigenetic influences originating from stromal cells in the immediate microenvironment may play a role in carcinogenesis. Determining the molecular mechanisms involved in stromal-stem cell interaction could provide critical insight into prostate development and disease progression, particularly with regard to their relationship to and influence on the putative cancer stem cell. METHODS: Prostate and bladder stromal cells prepared from tissue specimens were co-cultured with the pluripotent embryonal carcinoma cell line NCCIT. Transcriptome analysis was used to characterize NCCIT cell response to prostate or bladder signaling. RESULTS: A systems approach demonstrated that prostate stromal cells were capable of inducing gene expression changes in NCCIT through secreted factors. Induction led to a loss of embryonic stem cell markers, with concurrent up-regulation of many genes characteristic of stromal mesenchyme cells as well as some of epithelial and cancer stem cells. Bladder stromal signaling produced gene expression changes different from those of prostate signaling. CONCLUSIONS: This study indicates that paracrine stromal cell signaling can affect cancer stem cell response in an organ-specific manner and may provide insight for future development of treatment strategies such as differentiation therapy.

Identification of secreted glycoproteins of human prostate and bladder stromal cells by comparative quantitative proteomics.

BACKGROUND: Functional development of the prostate is governed by stromal mesenchyme induction and epithelial response. Stromal/epithelial signaling can be mediated through direct cell-cell contact and diffusible factors and their cell surface receptors. These inducers are likely secreted or membrane-associated extracellular proteins. Given the importance of intercellular communication, it is possible that diseases like cancer could arise from a loss of this communication. One approach to gain a molecular understanding of stromal cells is to identify, as a first step, secreted stromal signaling factors. We proposed to do this by comparative analysis between bladder and prostate. METHODS: Secreted proteins were identified from cultured normal prostate and bladder stromal mesenchyme cells by glycopeptide-capture method followed by mass spectrometry. Differences in protein abundance between prostate and bladder were quantified from calculated peptide ion current area (PICA) followed by Western validation. Functional and pathway analyses of the proteins were carried out by Gene Ontology (GO) and Teranode software. RESULTS: This analysis produced a list of 116 prostate and 84 bladder secreted glycoproteins with ProteinProphet probability scores > or =0.9. Stromal proteins upregulated in the prostate include cathepsin L, follistatin-related protein, neuroendocrine convertase, tumor necrosis factor receptor, and others that are known to be involved in signal transduction, extracellular matrix interaction, differentiation and transport. CONCLUSIONS: We have identified a number of potential proteins for stromal signaling and bladder or prostate differentiation program. The prostate stromal/epithelial signaling may be accomplished through activation of the ECM-receptor interaction, complement and coagulation cascades, focal adhesion and cell adhesion pathways.

Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes.

BACKGROUND: The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. The tumor-associated stroma is marked by increased expression of CD90/THY1. Isolation and characterization of these stromal cells could provide valuable insight into the biology of the tumor microenvironment. METHODS: Prostate CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between histologically normal and tumor-associated stromal cells. For comparison, stromal cells were also isolated and analyzed from the urinary bladder. RESULTS: The tumor-associated stromal cells were found to have decreased expression of genes involved in smooth muscle differentiation, and those detected in prostate but not bladder. Other differential expression between the stromal cell types included that of the CXC-chemokine genes. CONCLUSION: CD90+ prostate tumor-associated stromal cells differed from their normal counterpart in expression of multiple genes, some of which are potentially involved in organ development.