PhyloOncology: Understanding cancer through phylogenetic analysis.

Despite decades of research and an enormity of resultant data, cancer remains a significant public health problem. New tools and fresh perspectives are needed to obtain fundamental insights, to develop better prognostic and predictive tools, and to identify improved therapeutic interventions. With increasingly common genome-scale data, one suite of algorithms and concepts with potential to shed light on cancer biology is phylogenetics, a scientific discipline used in diverse fields. From grouping subsets of cancer samples to tracing subclonal evolution during cancer progression and metastasis, the use of phylogenetics is a powerful systems biology approach. Well-developed phylogenetic applications provide fast, robust approaches to analyze high-dimensional, heterogeneous cancer data sets. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

Oxymel: A systematic review of preclinical and clinical studies.

Background: Oxymel is a functional beverage with a rich historical background of use in multiple societies. Various simple and compound oxymels are prescribed in certain complementary and traditional medical systems, including traditional Persian Medicine. In recent years, numerous clinical and preclinical studies have been conducted in the pharmacy and food industry to investigate the efficacy of various oxymel formulations. This article aims to systematically review and summarize interventional studies on oxymel in both clinical research and animal models. Methods: Relevant articles were searched in Embase, MEDLINE, Web of Science Core Collection, Scopus, and Google Scholar from inception to July 2023 using the keyword "Oxymel" and its equivalents in other languages. Animal and human interventional studies were selected from the search results for review. Results: This review includes twenty studies, comprising twelve clinical trials, two case studies, and six animal studies. The most commonly reported actions of oxymel include positive effects on the cardiovascular system, as well as antioxidant and anti-inflammatory properties. Furthermore, compound oxymel formulations have demonstrated additional benefits depending on the inclusion of specific medicinal herbs. Conclusion: Based on our findings, oxymel appears to be a valuable functional food for healthy individuals and a potentially effective and safe treatment option for managing certain diseases such as asthma, obesity, and type 2 diabetes. However, further clinical trials with larger sample sizes and longer durations are needed to fully elucidate the potential side effects and benefits of both simple and compound oxymels in various disease states.

Stress biomarkers in medical students participating in a mind body medicine skills program.

Georgetown University School of Medicine offers an elective Mind-Body Medicine Skills (MBMS) course to medical students to promote self-care and self-awareness. Participating medical students reported better management of academic stress and well-being than non-participants. In this study, we sought to assess the stress-reducing effects of MBMS by measuring physiological changes in first-year medical students. Saliva samples were collected before (January, time 1 (T1)-pre-intervention) and upon completion of the course (May, time 2 (T2p)-post-intervention), as well as from non-participating medical students (May, time 2 (T2c)-control). The T2p and T2c collections coincided with the period of final examinations. Cortisol, dehydroepiandrosterone-sulfate (DHEA-S), testosterone and secretory immunoglobulin A (sIgA) were measured. The mean morning salivary cortisol at T2p was 97% of the mean at baseline T1 which was significantly lower than for T2c (2.4) (95% confidence interval (CI) 0.57-1.60, P = .001); DHEA-S showed similar pattern as cortisol where the T2p levels were significantly lower than T2c (P < .001) in both morning and evening collections. Testosterone ratio at T2p (0.85) was also lower than T2c (1.6) (95% CI 0.53-1.3, P = .01). sIgA levels were not statistically different. On direct comparison, the T2c and T2p means were significantly different for all cortisol, DHEA-S and testosterone values. Participants maintained their hormonal balance within the normal range throughout the academic semester while the control group showed significantly increased levels, probably exacerbated by the end of the semester exam stress. To our knowledge, this is the first study to assess the physiologic benefits of a MBMS program in medical students.

Medical students' attitudes to complementary and alternative medicine: further validation of the IMAQ and findings from an international longitudinal study.

BACKGROUND: Current research mainly employs cross-sectional designs to examine changes in medical students' attitudes towards complementary and alternative medicine (CAM). AIMS: This paper reports the findings of a longitudinal study to further validate the Integrative Medicine Attitude Questionnaire (IMAQ) and examine changes in medical students' attitudes over 3 years. METHODS: A total of 154 medical students from four schools in three countries completed a modified version of the IMAQ during their first (T1) and fourth year (T2). RESULTS: We established the validity of a three-factor model for the IMAQ: (1) attitudes towards holism; (2) attitudes towards the effectiveness of CAM therapies, and (3) attitudes towards introspection and the doctor-patient relationship. We found that IMAQ factor scores did not differ significantly from T1 to T2, emphasizing the relative stability in attitudes across time. Various student characteristics were significantly associated with IMAQ factor scores at T2: age, gender, CAM use, CAM education and school; and two variables (gender and CAM use) predicted changes in medical students' attitudes between T1 and T2. CONCLUSIONS: We urge medical educators to continue exploring medical students' attitude changes towards CAM and we provide examples of what further research is needed.

Metabolomics-Based Biosignatures of Prostate Cancer in Patients Following Radiotherapy.

Metabolomics offers new promise for research on prostate cancer (PCa) and its personalized treatment. Metabolomic profiling of radiation-treated PCa patients is particularly important to reveal their new metabolomic status, and evaluate the radiation effects. In addition, bioinformatics-integrated metabolomics-based approaches for disease profiling and assessment of therapy could help develop precision biomarkers in a context of PCa. We report mass spectrometry-based untargeted (global) serum metabolomics findings from patients with PCa (n = 55) before and after treatment with stereotactic body radiation therapy (SBRT), and intensity-modulated radiation therapy (IMRT) with SBRT, and using parsimony phylogenetic analysis. Importantly, the radiation-treated serum metabolome of patients represented a unique robust cluster on a cladogram that was distinct from the pre-RT metabolome. The altered radiation responsive serum metabolome was defined by predominant aberrations in the metabolic pathways of nitrogen, pyrimidine, purine, porphyrin, alanine, aspartate, glutamate, and glycerophospholipid. Our findings collectively suggest that global metabolomics integrated with parsimony phylogenetics offer a unique and robust systems biology analytical platform for powerful unbiased determination of radiotherapy (RT)-associated biosignatures in patients with PCa. These new observations call for future translational research for evaluation of metabolomic biomarkers in PCa prognosis specifically, and response to radiation treatment broadly. Radiation metabolomics is an emerging specialty of systems sciences and clinical medicine that warrants further research and educational initiatives.

A large-sample survey of first- and second-year medical student attitudes toward complementary and alternative medicine in the curriculum and in practice.

PURPOSE: To assess attitudes toward complementary and alternative medicine (CAM) and its place in the medical school curriculum and medical practice among preclinical students at Georgetown University School of Medicine (GUSOM), Washington, DC. METHOD: Two-hundred sixty-six first-year (n=111) and second-year (n=155) medical students rated their attitudes toward CAM and 15 CAM modalities in terms of personal use, inclusion in the curriculum, and use/utility in clinical practice. RESULTS: Nearly all (91%) students agreed that "CAM includes ideas and methods from which Western medicine could benefit"; more than 85% agreed that "knowledge about CAM is important to me as a student/future practicing health professional"; and more than 75% felt that CAM should be included in the curriculum. Among all students, the most frequently indicated level of desired training was "sufficient to advise patients about use," for 11 of the 15 modalities. The greatest level of training was wanted for acupuncture, chiropractic, herbal medicine, and nutritional supplements. The descriptions of CAM in future clinical practice that occurred most frequently were endorsement, referral, or provision of acupuncture, biofeedback, chiropractic, herbal medicine, massage, nutritional supplements, prayer, and meditation. CONCLUSIONS: Interest in and enthusiasm about CAM modalities was high in this sample; personal experience was much less prevalent. Students were in favor of CAM training in the curriculum to the extent that they could provide advice to patients; the largest proportions of the sample planned to endorse, refer patients for, or provide 8 of the 15 modalities surveyed in their future practice.

Promoting self-awareness and reflection through an experiential mind-body skills course for first year medical students.

BACKGROUND: This research examines student evaluations of their experience and attitudes in an 11 week mind-body skills course for first year medical students. AIMS: The aim is to understand the impact of this course on students' self-awareness, self-reflection, and self-care as part of their medical education experience. METHODS: This study uses a qualitative content analysis approach to data analysis. The data are 492 verbatim responses from 82 students to six open-ended questions about the students' experiences and attitudes after a mind-body skills course. These questions queried students' attitudes about mind-body medicine, complementary medicine, and their future as physicians using these approaches. RESULTS: The data revealed five central themes in students' responses: connections, self discovery, stress relief, learning, and medical education. CONCLUSIONS: Mind-body skills groups represent an experiential approach to teaching mind-body techniques that can enable students to achieve self-awareness and self-reflection in order to engage in self-care and to gain exposure to mind-body medicine while in medical school.

Cancer-related overexpression of the peripheral-type benzodiazepine receptor and cytostatic anticancer effects of Ginkgo biloba extract (EGb 761).

The peripheral-type benzodiazepine receptor (PBR) is an 18-kDa high affinity drug- and cholesterol-binding protein that is involved in various cell functions, including cell proliferation and apoptosis. PBR was shown to be overexpressed in certain types of malignant human tumors and cancer cell lines, correlating with enhanced tumorigenicity and cell proliferation rates. The present study was conducted in order to further define the role of PBR in cancer and to extend our recent findings regarding the possible anticancer effects of the standardized Ginkgo biloba extract EGb 761. Treatment with EGb 761 decreased PBR mRNA levels and inhibited the proliferation of breast, glioma and hepatocarcinoma cell lines, further corroborating our previous contention that its mechanism of action is through the modification of PBR expression. In vivo treatment with Ginkgo biloba extract led to dose-dependent decreases in xenograft growth of both MDA-MB-231 breast cancer and U-87 glioma cell lines in nude mice, although the effects were not maintained after 50 days of treatment in the latter. The results obtained in MDA-MB-231 xenografts indicated pronounced inhibition of tumor growth, verified by MRI imaging. These results were obtained using a modified experimental protocol where the animals were treated with the extract before cell inoculation. Although an exact role for PBR in relation to the initiation and progression of various types of cancer remains to be defined, our results indicate that PBR overexpression in certain cancer cells is related to an aggressive phenotype. Since EGb 761 treatment opposes this aggressive phenotype by decreasing PBR overexpression, it could be useful in preventing or treating cancer invasiveness and metastasis.

Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models.

The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (P<.01). The difference in reduction is likely due to the specific doubling time of each cell line. No effect was observed on MDA-MB-231 human breast cancer cells. Thuja occidentalis and Conium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata-treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.

China's Other Medical Systems: Recognizing Uyghur, Tibetan, and Mongolian Traditional Medicines.

BACKGROUND: Traditional Chinese medicine, as it is understood and adopted by those with a growing interest in complementary and alternative practices to biomedicine, is often used as an umbrella term for traditional medical practices from regions within and bordering the People's Republic of China. However, there are multiple distinct medical traditions in China, including that of the Uyghurs, Tibetans, and Mongolians. OBJECTIVE: It is important to recognize the commonalities and differences of these unique systems of medicine practiced by the 3 different cultures among China's borders. METHODS: Through an in-depth analysis of the individual beliefs and theories that form the foundation of each system, we trace the origins of the concepts that were synthesized into the Uyghur, Tibetan, and Mongolian medical systems. Furthermore, we compare diagnostic techniques and contrast treatment modalities among the 3 systems. DISCUSSION: We discuss humoral theory, constitution theory, elemental theory, organ theory, and yin and yang theory. We find that imbalance is the common cause of disease or illness, but the conditions and external factors that explain such imbalances differ among the Uyghur, Tibetan, and Mongolian systems. Through these comparisons, we seek to highlight the unique beliefs, practices, and treatments utilized by these cultures. CONCLUSION: The features and attributes, while not exclusive to each population, are nonetheless uniquely synthesized by each system and thus demonstrate the distinct nature of Uyghur, Tibetan, and Mongolian medical systems.

Study of Clinical Survival and Gene Expression in a Sample of Pancreatic Ductal Adenocarcinoma by Parsimony Phylogenetic Analysis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the rapidly growing forms of pancreatic cancer with a poor prognosis and less than 5% 5-year survival rate. In this study, we characterized the genetic signatures and signaling pathways related to survival from PDAC, using a parsimony phylogenetic algorithm. We applied the parsimony phylogenetic algorithm to analyze the publicly available whole-genome in silico array analysis of a gene expression data set in 25 early-stage human PDAC specimens. We explain here that the parsimony phylogenetics is an evolutionary analytical method that offers important promise to uncover clonal (driver) and nonclonal (passenger) aberrations in complex diseases. In our analysis, parsimony and statistical analyses did not identify significant correlations between survival times and gene expression values. Thus, the survival rankings did not appear to be significantly different between patients for any specific gene (p > 0.05). Also, we did not find correlation between gene expression data and tumor stage in the present data set. While the present analysis was unable to identify in this relatively small sample of patients a molecular signature associated with pancreatic cancer prognosis, we suggest that future research and analyses with the parsimony phylogenetic algorithm in larger patient samples are worthwhile, given the devastating nature of pancreatic cancer and its early diagnosis, and the need for novel data analytic approaches. The future research practices might want to place greater emphasis on phylogenetics as one of the analytical paradigms, as our findings presented here are on the cusp of this shift, especially in the current era of Big Data and innovation policies advocating for greater data sharing and reanalysis.

Multischool, international survey of medical students' attitudes toward "holism".

PURPOSE: Core and optional courses of study in complementary and alternative medicine (CAM) are being incorporated into medical curricula. The authors carried out this study to validate a tool to examine students' attitudes toward holism and CAM and explore the relationships between their attitudes and other demographic and education-related characteristics in a large, multischool, international sample of medical students. METHOD: In 2003 the authors used a modified version of the Integrated Medicine Attitude Questionnaire (IMAQ) to survey students at a total of six medical schools in the United Kingdom, New Zealand, Canada, the United States, and Hong Kong, China. A three-factor model was tested using confirmatory factor analysis, and the internal consistency of the factors were identified using Cronbach's alpha coefficients. A multiple-indicator multiple-cause (MIMIC) analysis was carried out to determine the relationship between IMAQ factors and student characteristics. RESULTS: The authors validated a three-factor model for the IMAQ: (1) attitudes toward holism, (2) attitudes toward the effectiveness of CAM, and (3) attitudes toward introspection and the doctor-patient relationship. Cronbach's alpha coefficients ranged from .41 to .71. The MIMIC model indicated that various background variables were associated with IMAQ factors (gender, race/ethnicity, and school), depending on whether students had previously visited a CAM practitioner and whether students were willing to undertake a special study module in CAM. CONCLUSIONS: Further development work on the IMAQ is required and qualitative research to verify and examine the reasons behind the relationships found in this study between students' attitudes to holism and their demographic and education-related characteristics.

Computational Tools for Parsimony Phylogenetic Analysis of Omics Data.

High-throughput assays from genomics, proteomics, metabolomics, and next generation sequencing produce massive omics datasets that are challenging to analyze in biological or clinical contexts. Thus far, there is no publicly available program for converting quantitative omics data into input formats to be used in off-the-shelf robust phylogenetic programs. To the best of our knowledge, this is the first report on creation of two Windows-based programs, OmicsTract and SynpExtractor, to address this gap. We note, as a way of introduction and development of these programs, that one particularly useful bioinformatics inferential modeling is the phylogenetic cladogram. Cladograms are multidimensional tools that show the relatedness between subgroups of healthy and diseased individuals and the latter's shared aberrations; they also reveal some characteristics of a disease that would not otherwise be apparent by other analytical methods. The OmicsTract and SynpExtractor were written for the respective tasks of (1) accommodating advanced phylogenetic parsimony analysis (through standard programs of MIX [from PHYLIP] and TNT), and (2) extracting shared aberrations at the cladogram nodes. OmicsTract converts comma-delimited data tables through assigning each data point into a binary value ("0" for normal states and "1" for abnormal states) then outputs the converted data tables into the proper input file formats for MIX or with embedded commands for TNT. SynapExtractor uses outfiles from MIX and TNT to extract the shared aberrations of each node of the cladogram, matching them with identifying labels from the dataset and exporting them into a comma-delimited file. Labels may be gene identifiers in gene-expression datasets or m/z values in mass spectrometry datasets. By automating these steps, OmicsTract and SynpExtractor offer a veritable opportunity for rapid and standardized phylogenetic analyses of omics data; their model can also be extended to next generation sequencing (NGS) data. We make OmicsTract and SynpExtractor publicly and freely available for non-commercial use in order to strengthen and build capacity for the phylogenetic paradigm of omics analysis.

Identification of the adrenocorticotropin and ginkgolide B-regulated 90-kilodalton protein (p90) in adrenocortical cells as a serotransferrin precursor protein homolog (adrenotransferrin).

Two-dimensional electrophoresis (2D-PAGE) of metabolically labeled adrenocortical proteins, identified a series of spots at a molecular size of 90 kDa [isoelectric point (pI) 6.8-7.1; p90] that was induced by ACTH, but whose intensity was reduced in cells obtained from animals treated with an extract of Ginkgo biloba (EGb 761) and its purified component ginkgolide B (GKB). We have now identified p90. GKB (2 mg/kg x d, i.p.) was administered to rats for 8 d. Adrenocortical cells were prepared and stimulated with ACTH for 3 h. Cells obtained from saline-treated rats responded to ACTH by producing high amounts of corticosterone, an effect that was inhibited in cells obtained from GKB-treated animals. Samples were fractionated by 2D-PAGE and matrix-assisted laser desorption ionization mass spectrometry analysis of the p90 spots isolated from the gels revealed sequences sharing identity with the serotransferrin precursor protein. Further PCR screening of a rat adrenal cDNA library identified a sequence with a high degree of homology (79%) to serotransferrin precursor protein, and a lesser degree to rat transferrin (54%) and human melanotransferrin (32.8%). p90, in 2D-PAGE immunoblots, was also recognized by a monoclonal antibody raised against human 97-kDa melanotransferrin. Iron binding assays with rat adrenal cortex extracts further identified a 90-kDa melanotransferrin immunoreactive protein binding iron, suggesting that the identified protein, which we name "adrenotransferrin," may have iron-binding activity. This is the first report describing the presence of a serotransferrin precursor protein homolog belonging to the transferrin family and sharing epitopes with melanotransferrin in the adrenal, its induction by ACTH, and sensitivity to GKB.

Transcriptional suppression of the adrenal cortical peripheral-type benzodiazepine receptor gene and inhibition of steroid synthesis by ginkgolide B.

Treatment of rats and adrenocortical cells with ginkgolide B (GKB), a purified component of Ginkgo biloba leaf extracts, reduces the mRNA, protein, and ligand-binding levels of the adrenal peripheral-type benzodiazepine receptor (PBR), a mitochondrial cholesterol-binding protein, leading to decreased corticosteroid synthesis. In the Y1 adrenocortical cell line, GKB reduced both PBR levels and cyclic AMP-induced steroid formation. In these cells, GKB, but not various steroids and vitamins, reduced the expression of a reporter gene driven by the DNA sequence -624/-513 relative to the transcription start site of the PBR encoding gene. GKB treatment did not affect the SV40 promoter and increased the cytochrome P450 17alpha-hydroxylase gene promoter driven expression of the reporter gene. Electrophoretic mobility shift assays (EMSAs) indicated the presence of a functional transcriptional element bound to the -624/-513 DNA fragment. This GKB-induced inhibition of PBR was mediated by an interaction with a transcription factor that binds to the -636/-616 PBR-promoter region. Deletion or mutation of this sequence eliminated the DNA-protein interaction and the inhibitory effect of GKB on PBR gene transcription. This DNA-binding protein could be detected in nuclear extracts of rat brain, liver, and testis, but not kidney. It is also present in the human adrenal glands. However, the inhibitory effect following GKB treatment could be seen only in the adrenal glands. These results demonstrate that the GKB-activated inhibition of glucocorticoid production is due to a specific transcriptional suppression of the adrenal PBR gene and suggest that GKB might serve as a pharmacological tool to control excess glucocorticoid formation.

Gene and protein profiling of the response of MA-10 Leydig tumor cells to human chorionic gonadotropin.

Activation of the steroidogenic machinery by peptide hormones involves a number of steps for transmitting signals from the plasma membrane to mitochondria in a spatially and temporally coordinated manner. Although key proteins mediating the hormonal signal have been identified, recent data suggest that the pathway might involve more complex protein-protein and protein-lipid interactions. Genomic and proteomic methods of analysis, namely the Affymetrix Murine Genome U74A v2 GeneChip and the BD PowerBlot Western Array, were used to identify human chorionic gonadotropin (hCG)-induced changes in mRNA and protein of MA-10 Leydig tumor cells that parallel the increase seen in progesterone synthesis. To analyze the massive amount of data that was generated, a comprehensive protein information matrix summarizing the features of each gene or protein, including its known properties, as well as annotations derived by homology-based functional inference, was developed. Of the genes examined by Affymetrix array, approximately 79 were differentially expressed and of gene products examined by PowerBlot, 9 were differentially expressed (above twofold). Changes in the expression of selected transcripts of interest were confirmed using real-time quantitative polymerase chain reaction and immunoblot analyses. Collectively, these results indicate that hormonal regulation of steroidogenesis is a complex phenomenon, involving proteins that participate in various known and novel pathways, which are implicated in transmitting signals from the plasma membrane to mitochondria and nucleus.

Analyzing heterogeneous complexity in complementary and alternative medicine research: a systems biology solution via parsimony phylogenetics.

Systems biology offers cutting-edge tools for the study of complementary and alternative medicine (CAM). The advent of 'omics' techniques and the resulting avalanche of scientific data have introduced an unprecedented level of complexity and heterogeneous data to biomedical research, leading to the development of novel research approaches. Statistical averaging has its limitations and is unsuitable for the analysis of heterogeneity, as it masks diversity by homogenizing otherwise heterogeneous populations. Unfortunately, most researchers are unaware of alternative methods of analysis capable of accounting for individual variability. This paper describes a systems biology solution to data complexity through the application of parsimony phylogenetic analysis. Maximum parsimony (MP) provides a data-based modeling paradigm that will permit a priori stratification of the study cohort(s), better assessment of early diagnosis, prognosis, and treatment efficacy within each stratum, and a method that could be used to explore, identify and describe complex human patterning.

The EPI bioassay identifies natural compounds with estrogenic activity that are potent inhibitors of androgenic pathways in human prostate stromal and epithelial cells.

The reactive stromal phenotype is an important factor for prostate cancer progression and may be a new target for treatment and prevention. A new high efficiency preclinical protocol, the EPI bioassay, reflects the interaction of endocrine, paracrine and immune, (EPI) factors on induced androgen metabolism in human prostate reactive stroma. The bioassay is based on co-culturing human primary prostate stromal cells and LAPC-4 prostatic adenocarcinoma cells in a downscaled format of 96-well-plates for testing multiple doses of multiple target compounds. Metabolism of dehydroepiandrosterone (DHEA) with or without TGFß1-induced stimulation (D+T) of the reactive stroma phenotype was assessed by increased testosterone in the media and PSA production of the epithelial prostate cancer cells. Using the non-metabolizable androgen R1881, effects from direct androgen action were distinguished from stromal androgen production from DHEA. Stromal cell androgenic bioactivity was confirmed using conditioned media from D+T-treated stromal cell monocultures in an androgen-inducible AR screening assay. We further showed that both agonists to estrogen receptor (ER), DPN (ERß) and PPT (ERα), as well as estrogenic natural compounds including soy isoflavones attenuated D+T-induced PSA production. Studies with the pure ER agonists showed that activating either ERα or ERß could inhibit both D+T-mediated and R1881-mediated PSA production with the D+T effect being more pronounced. In conclusion, natural compounds with estrogenic activity and pure ER agonists are very potent inhibitors of stromal conversion of DHEA to androgenic metabolites. More studies are needed to characterize the mechanisms involved in estrogenic modulation of the endocrine-immune-paracrine balance of the prostate microenvironment.

Acupuncture at ST36 prevents chronic stress-induced increases in neuropeptide Y in rat.

Chronic stress, as seen in post-traumatic stress disorder, can exacerbate existing diseases. Electroacupuncture (EA) has been proposed to treat chronic stress, although information on its efficacy or mechanism(s) of action is limited. While many factors contribute to the chronic stress response, the sympathetic peptide, neuropeptide Y (NPY), has been shown to be elevated in chronic stress and is hypothesized to contribute to the physiological stress response. Our objective was to determine if EA at acupuncture point stomach 36 (ST(36)) is effective in mitigating cold stress-induced increase in NPY in rats. Both pretreatment and concomitant treatment with EA ST(36) effectively suppressed peripheral and central NPY after 14 d of cold stress (P < 0.05). The effect was specific, as NPY in Sham-EA rats was not different than observed in stress-only rats. Additionally, the effect of EA ST(36) was long-lasting, as NPY levels remained suppressed despite early cessation of EA ST(36), while exposure to cold stress was continued. In the paraventricular nucleus (PVN), it was notable that changes in NPY mirrored plasma NPY levels, and that the significant elevation in PVN Y1 receptor observed with stress was also prevented with EA ST(36). The findings indicate that EA ST(36) is effective in preventing one of the sympathetic pathways stimulated during chronic stress, and thus may be a useful adjunct therapy in stress-related disorders.

Endometriosis gene expression heterogeneity and biosignature: a phylogenetic analysis.

Endometriosis is a multifactorial disease with poorly understood etiology, and reflecting an evolutionary nature where genetic alterations accumulate throughout pathogenesis. Our objective was to characterize the heterogeneous pathological process using parsimony phylogenetics. Gene expression microarray data of ovarian endometriosis obtained from NCBI database were polarized and coded into derived (abnormal) and ancestral (normal) states. Such alterations are referred to as synapomorphies in a phylogenetic sense (or biomarkers). Subsequent gene linkage was modeled by Genomatix BiblioSphere Pathway software. A list of clonally shared derived (abnormal) expressions revealed the pattern of heterogeneity among specimens. In addition, it has identified disruptions within the major regulatory pathways including those involved in cell proliferation, steroidogenesis, angiogenesis, cytoskeletal organization and integrity, and tumorigenesis, as well as cell adhesion and migration. Furthermore, the analysis supported the potential central involvement of ESR2 in the initiation of endometriosis. The pathogenesis mapping showed that eutopic and ectopic lesions have different molecular biosignatures.