Med. Sci., Volume 4, Issue 3 (September 2016) – 5 articles

The aim of this study was to investigate prevalence and related factors of androgen receptor (AR) expression in Thai breast cancer patients. A descriptive study was done in 95 patients, who were admitted to Charoenkrung Pracharak Hospital, Bangkok (2011–2013). Statistical relationships were examined between AR protein expression, tumor status, and patient characteristics. Compared with those from Western countries, ethnic Thai patients were younger at age of diagnosis and had a higher proliferative index (high Ki-67 expression), which indicates unfavorable prognosis. In addition, 91% of the Thai breast tumors that were positive for any of the following receptors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) also expressed the AR protein, while in triple negative breast tumors only 33% were AR positive. ER and PR expression was positively related with AR expression, while AR expression was inversely correlated to Ki-67 expression. AR status was strongly correlated with ER and PR status in Thai patients. There is an inverse relationship between Ki-67 and AR, which suggests that AR may be a prognostic factor for breast cancer. Full article

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders with a severe medical and social impact. Further insights from clinical and scientific studies are essential to develop effective therapies. Various stresses on the endoplasmic reticulum (ER) cause unfolded/misfolded proteins to aggregate, initiating unfolded protein responses (UPR), one of which is the induction of neuronal cell death. Some of the pathogenic factors for AD and PD are associated with UPR. ER molecules such as ubiquitin ligases (E3s) and chaperones are also produced during UPR to degrade and refold aberrant proteins that accumulate in the ER. In this review, we examine the role of HMG-CoA reductase degradation protein 1 (HRD1) and the chaperone protein-disulfide isomerase (PDI), which are both produced in the ER in response to stress. We discuss the importance of HRD1 in degrading amyloid precursor protein (APP) and Parkin-associated endothelin receptor-like receptor (Pael-R) to protect against neuronal death. PDI and the chemical chaperone 4-phenyl-butyrate also exert neuroprotective effects. We discuss the pathophysiological roles of ER stress, UPR, and the induction and neuroprotective effects of HRD1 and PDI, which may represent significant targets for novel AD and PD therapies. Full article

Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize environmental chemicals that could alter the expression and function of the nigrostriatal dopamine system. Of particular interest is the neurotoxicological effect of perfluorinated compounds, such as perfluorooctane sulfonate (PFOS), which has been demonstrated to alter aspects of dopamine signaling. Using in vitro approaches, we have elaborated these initial findings to demonstrate the neurotoxicity of PFOS to the SH-SY5Y neuroblastoma cell line and dopaminergic primary cultured neurons. Using an in vivo model, we did not observe a deficit to dopaminergic terminals in the striatum of mice exposed to 10 mg/kg PFOS for 14 days. However, subsequent exposure to the selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly reduced the expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH), and resulted in an even greater reduction in DAT expression in animals previously exposed to PFOS. These findings suggest that PFOS is neurotoxic to the nigrostriatal dopamine circuit and this neurotoxicity could prime the dopamine terminal to more extensive damage following additional toxicological insults. Full article

Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations (CNAs), have been identified in the pathogenesis of cervical carcinomas in non-Mexican Americans. Thus, the purpose of this study was to investigate CNAs in association with cervical cancer in the Mexican American population. We conducted a pilot study of genome-wide CNA analysis using 2.5 million markers in four diagnostic groups: reference (n = 125), low grade dysplasia (cervical intraepithelial neoplasia (CIN)-I, n = 4), high grade dysplasia (CIN-II and -III, n = 5) and invasive carcinoma (squamous cell carcinoma (SCC), n = 5) followed by data analyses using Partek. We observed a statistically-significant difference of CNA burden between case and reference groups of different sizes (>100 kb, 10–100 kb and 1–10 kb) of CNAs that included deletions and amplifications, e.g., a statistically-significant difference of >100 kb deletions was observed between the reference (6.6%) and pre-cancer and cancer (91.3%) groups. Recurrent aberrations of 98 CNA regions were also identified in cases only. However, none of the CNAs have an impact on cancer progression. A total of 32 CNA regions identified contained tumor suppressor genes and oncogenes. Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (p < 0.05) using Kyoto Encyclopedia of Genes and Genomes (KEGG). This is the first report of CNAs identified for cervical cancer in the U.S. Latino population using high density markers. We are aware of the small sample size in the study. Thus, additional studies with a larger sample are needed to confirm the current findings. Full article

The renal functions and structure in sickle cell anaemia (SCA) patients may be affected by chronic haemodynamic changes and consequences of vaso-occlusive events in the renal medulla. Few reports on neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios in SCA patients in Africans exist in the literature. This study correlates the values of NLR and PLR with measured traditional inflammatory markers in SCA patients with and without proteinuria and impaired kidney function (defined in this study as estimated glomerular filtration rate (eGFR), less than 60 mL/min/1.73 m². Full blood count, C-reactive protein (CRP), and fibrinogen were assayed in 150 SCA patients and 50 control subjects using Coulter Haematology analyser (CELL DYE 37000) and ELISA method, respectively. The NLR and PLR were calculated by dividing absolute neutrophil or platelet counts by absolute lymphocyte count. Fibrinogen, CRP, NLR, and PLR increased progressively (p < 0.001) in SCA patients with or without proteinuria, with the highest values seen in those with impaired renal function. NLR correlated positively with CRP and fibrinogen in SCA patients without proteinuria (p < 0.001), with proteinuria (p < 0.001), and impaired renal function (p < 0.05). A positive relationship was also observed between NLR and fibrinogen in the control subjects. The need to determine cut-off values for these leukocyte ratios to be used in identifying those patients at risk and in the general management of SCA patients is suggested. Full article