Genistein chemoprevention of prostate cancer in TRAMP mice

Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. Genistein, the predominant phytoestrogen in soy food, has been proposed as a potential chemopreventive agent due to its anti-estrogen and tyrosine kinase inhibitory effects. To determine the most effective period for genistein chemoprevention, the Transgenic adenocarcinoma mouse prostate (TRAMP) model was used. The treatments were 250 mg genistein/kg AIN-76A diet 1) prepubertally only, 2) in adulthood only or 3) through out life. Controls received AIN-76A diet. By 28 weeks of age, 100% TRAMP mice fed control diet developed prostatic intraepithelial neoplasia (PIN) or adenocarcinomas with 6%, 16%, 44% and 34% developing high grade PIN, well differentiated, moderately differentiated and poorly differentiated prostatic adenocarcinomas, respectively. Prepubertal only (1–35 days postpartum) and adult only genistein treatments (12 – 28 weeks) resulted in 6% and 29% decreases in poorly-differentiated cancerous lesions compared with controls, respectively. The most significant effect was seen in the TRAMP mice exposed to genistein throughout life (1–28 weeks) with a 50% decrease in poorly-differentiated cancerous lesions. In a separate experiment in castrated TRAMP mice, dietary genistein suppressed the development of advanced prostate cancer by 35% compared with controls. Of the tumors that developed in castrated TRAMP mice, 100% were poorly-differentiated in contrast to the 37% of noncastrated TRAMP mice that developed poorly-differentiated tumors. ICI 182,780 (ICI), genistein and estrogen down-regulated androgen receptor (AR), estrogen receptor alpha (ER-α) and progesterone receptor (PR) in the prostates of C57BL/6 mice, and act independently of ER. Our data obtained in intact and castrated transgenic mice suggest that genistein may be a promising chemopreventive agent against androgen-dependent and independent prostate cancers

Evaluation of Biochemical Parameters for Sickle Cell Anemic Children at Kassala City, Eastern Sudan

Background: Sickle cell disease (SCD) is an inherited disease caused by gene mutation. Many investigators reported that Eastern Sudan has rich SCD and also an association with biochemical parameters such as liver and renal function tests. Objective: The present study was to assess the plasma biochemical parameters such as urea, creatinine and sodium (Na) and potassium (K) total protein, albumin, Bilirubin, Aspartate Transaminase (AST), Alanine Transaminase (ALT) and Alkaline Phosphatase (ALP) in SCD as case group and apparently healthy persons as control group. Materials and Methods:The study was conducted at Kassala Teaching Hospital, Kassala city, Eastern Sudan. This study was carried during December 2019 to January 2020. A total of 100 subjects enrolled in this study, 50 patients with SCD as case group and 50 apparently healthy as control group. The plasma biochemical parameters were estimated using Biosystem-350(Semi automated chemistry analyzer), and plasma Na and K were estimated using Easylyte. The data was analyzed using SPSS version (23). Results:Study populations were matched age and sex, the age ranged from 5 to 15 years with their average age 8years. The plasma Na was insignificance difference in case compared to control group. The plasma K, urea and creatinine (p=0.039) were significantly increase compared to control group. Also the plasma total protein, albumin, Bilirubin, creatinine, AST, ALT and ALP were significantly increase in case group compared to control group. The age was strong association into plasma urea(r=0.583, p=.000) and plasma crearinine (r=0.759, p=.000). The negative correlation between plasma Na and plasma urea (r= -.335, p=0.017). There was positive correlation between plasma urea and creatinine (r=0.332, p=0.018).  Their strong association between plasma Bilirubin and ALP activity (r= .563, P=.000), and also their strongly association between liver enzymes plasma level among SCD patients (r=.873, 381, 563, P= .000, .006, 000). Conclusion:The study concluded that, significance increased in plasma K, urea creatinine, plasma total protein, and albumin, Bilirubin, AST, ALT and ALP. Strong association between age and    plasma urea, creatinine, and the negative correlation between plasma Na and plasma urea and also positive correlation between plasma urea and creatinine. There were positive correlation between plasma urea and creatinine.  Their strong association between plasma bilirubin and ALP levels and also their strongly association between liver enzymes levels among SCD patients. Observation of the study concludes the biochemical abnormality play a significant role in sickle cell patient’s physiopathology and can be used to management of the disease

Interactions between Cells with Distinct Mutations in c-MYC and Pten in Prostate Cancer

In human somatic tumorigenesis, mutations are thought to arise sporadically in individual cells surrounded by unaffected cells. This contrasts with most current transgenic models where mutations are induced synchronously in entire cell populations. Here we have modeled sporadic oncogene activation using a transgenic mouse in which c-MYC is focally activated in prostate luminal epithelial cells. Focal c-MYC expression resulted in mild pathology, but prostate-specific deletion of a single allele of the Pten tumor suppressor gene cooperated with c-MYC to induce high grade prostatic intraepithelial neoplasia (HGPIN)/cancer lesions. These lesions were in all cases associated with loss of Pten protein expression from the wild type allele. In the prostates of mice with concurrent homozygous deletion of Pten and focal c-MYC activation, double mutant (i.e. c-MYC+;Pten-null) cells were of higher grade and proliferated faster than single mutant (Pten-null) cells within the same glands. Consequently, double mutant cells outcompeted single mutant cells despite the presence of increased rates of apoptosis in the former. The p53 pathway was activated in Pten-deficient prostate cells and tissues, but c-MYC expression shifted the p53 response from senescence to apoptosis by repressing the p53 target gene p21Cip1. We conclude that c-MYC overexpression and Pten deficiency cooperate to promote prostate tumorigenesis, but a p53-dependent apoptotic response may present a barrier to further progression. Our results highlight the utility of inducing mutations focally to model the competitive interactions between cell populations with distinct genetic alterations during tumorigenesis

Chronic Oral Exposure to Bisphenol A Results in a Nonmonotonic Dose Response in Mammary Carcinogenesis and Metastasis in MMTV-erbB2 Mice

Background: Bisphenol A (BPA) is a synthetic compound used to produce plastics and epoxy resins. BPA can leach from these products in appreciable amounts, resulting in nearly ubiquitous daily exposure to humans. Whether BPA is harmful to humans, especially when administered orally in concentrations relevant to humans, is a topic of debate

Identification of Distinct Heterogenic Subtypes and Molecular Signatures Associated with African Ancestry in Triple Negative Breast Cancer Using Quantified Genetic Ancestry Models in Admixed Race Populations

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n = 42) and European American (EA, n = 33) women. RNA sequencing data were analyzed to measure changes in genome-wide expression, and we utilized logistic regressions to identify ancestry-associated gene expression signatures. Using SNVs identified from our RNA sequencing data, global ancestry was estimated. We identified 156 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like two tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated

Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test

Background. Determining cervical precancer risk among human immunodeficiency virus (HIV)–infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices