Immunohistochemical Study of Androgen Receptor Expression in Estrogen Receptor-Negative Invasive Breast Carcinoma and its Relation with Clinicopathologic Factors

BACKGROUND: Estrogen receptor (ER)-negative breast carcinomas lack the expression of ER and they have no targeted hormone therapies. The androgen receptor (AR) is a newly emerge biomarker. Detecting AR in these tumors may provide a target for future therapies. AIM: The aim of the study is to examine the immunohistochemical expression profiles of AR protein in ER-negative invasive breast carcinomas and to assess the relation between AR expression and the clinicopathologic factors such as age, tumor size, tumor grade, tumor type, immunohistochemical type, lymph node status, and Ki67 expression. METHODS: Sixty paraffin blocks of ER-negative invasive breast carcinoma cases were stained immunohistochemically by AR. Positive expression was defined as ≥1% nuclear staining. RESULTS: AR positivity was detected in 55% of the studied cases. The positive cases were scored by H-score with a median=117, and a range of 3–285 and by Allred score with a median=7, and a range of 3-8. AR is expressed in 60.9% of triple-negative breast carcinoma cases. AR expression was higher in older age, and there were significant positive correlations between the degree of AR expression (AR%, AR intensity, and H-score) and age (p=0.050, 0.007, 0.033, respectively). There was non-significant negative correlation between Ki67% and the degree of AR expression (AR%, AR intensity, H-score, and Allred score). Regarding different histological types, tumor grade, tumor size, lymph node status, and immunohistochemical types, there was no significant difference between AR positive and AR negative cases. CONCLUSION: AR is frequently expressed in ER-negative invasive breast carcinoma; especially in older age, and in a large number of triple-negative subtypes. This may give chance to benefit from future AR target therapy. We recommend further research work on AR expression in the special histologic subtypes of ER-negative breast carcinoma and in the triple negative group

Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals

<p>Abstract</p> <p>Background</p> <p>Metformin protection against cancer risk in Orientals is uncertain. We examined the possible metformin effect on total, esophageal, gastric, colorectal (CRC), hepatocellular (HCC) and pancreatic cancers in a Taiwanese cohort.</p> <p>Methods</p> <p>A representative sample of 800,000 was drawn from the Taiwanese National Health Insurance data of 2000. A cohort of 480,984 participants 20 years or older, diabetes-cancer-free on 1st January 2000 was formed and categorized as four groups by DM and metformin usage status. Eligible incident cancer events had to occur one year after the index date until the end of 2007. The Cox proportional-hazards model evaluated relative risk of cancer for treated DM patients with or without metformin. The covariates included age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index (CCI) score and metformin exposure dosage and duration.</p> <p>Results</p> <p>With diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total, CRC and HCC. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels but to varying degrees depending on gender and cancer type (CRC in women, liver in men). Adjustment for other oral anti-hyperglycemic agents usage and CCI made the benefit of metformin more evident [hazard ratios (95% confidence intervals): total 0.12 (0.08-0.19), CRC 0.36 (0.13-0.98), liver 0.06 (0.02-0.16), pancreas 0.15 (0.03-0.79)]. There was a significant gender interaction with metformin in CRC which favored women. Metformin dosage for a significant decrease in cancer incidence was ≤500 mg/day.</p> <p>Conclusions</p> <p>Metformin can reduce the incidences of several gastroenterological cancers in treated diabetes.</p

Hydrogen-free liquid-helium recovery plants: the solution for low-temperature flow impedance blocking

Under the terms of the Creative Commons Attribution license.-- et al.The blocking of fine-capillary tubes used as flow impedances in He4 evaporation cryostats to achieve temperatures below 4.2 K is generally attributed to nitrogen or air impurities entering these tubes from the main bath. The failure of even the most rigorous low-temperature laboratory best practices aimed at eliminating the problem by maintaining the cleanliness of the helium bath and preventing impurities from entering the capillary tubes suggests that a different cause is responsible for the inexplicable reduction of impedance flow. Many low-temperature research laboratories around the world have suffered this nuisance at a considerable financial cost due to the fact that the affected systems have to be warmed to room temperature in order to recover their normal low-temperature operation performance. Here, we propose an underlying physical mechanism responsible for the blockages based upon the freezing of molecular H2 traces present in the liquid-helium bath. Solid H2 accumulates at the impedance low-pressure side, and, after some time, it produces a total impedance blockage. The presence of H2 traces is unavoidable due its occurrence in the natural gas wells where helium is harvested, forcing gas suppliers to specify a lower bound for impurity levels at about 100 ppb even in high-grade helium. In this paper, we present a simple apparatus to detect hydrogen traces present in liquid helium and easily check the quality of the liquid. Finally, we propose a solution to eliminate the hydrogen impurities in small- and large-scale helium recovery plants. The solution has been implemented in several laboratories that previously experienced a chronic occurrence of blocking, eliminating similar occurrences for more than one year.The authors are greatly appreciative and acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the INNPACTO Projects No. IPT-2012-0442-420000 and No. MAT2015-64083-R, in addition to European Union FEDER funds.Peer Reviewe

Prophylactic effects of biogenic selenium nanoparticles on acute toxoplasmosis: An in vivo study

Background: In this investigation, the in vivo efficacy and safety of biogenic selenium nanoparticles (SeNPs) are assessed against acute toxoplasmosis caused by Toxoplasma gondii (Sarcocystidae) in the mice. Methods: Male NMRI mice were orally treated with normal saline (control group) and SeNPs at the doses of 5 and 10 mg/kg once a day for 14 days. On the 15th day, the mice were infected with 104 tachyzoites of T. gondii RH strain by the intraperitoneal route. The mortality rate and parasite load were determined in the infected mice. The mRNA levels of IFN-γ, IL10, IL12, and inducible nitric oxide synthase were also examined in the infected mice by quantitative real-time PCR. Results: The rate of mortality in the infected mice receiving SeNPs at the doses of 5 and 10 mg/kg compared with the mice in the control group was 100 on the 9 and 10 days after the administration. The mean number of tachyzoites in the infected mice receiving SeNPs was significantly lower than that in the control group. No significant difference (p &gt; 0.05) was found in the biochemical parameters between the mice treated with SeNPs and the mice in the control group. The results revealed that mRNA levels significantly improved in the infected mice treated with SeNPs compared with those in the control group. Conclusion: Findings of the present investigation showed the considerable efficacy of SeNPs with no important toxicity for curing acute toxoplasmosis in the mice model. However, further studies are needed to clarify the accurate anti-Toxoplasma mechanisms of SeNPs. © 2020 The Author(s

In vitro analysis of antiangiogenic activity of fungi isolated from clinical cases of equine keratomycosis.

OBJECTIVE: The goal of this project was to explore the possibility that fungal organisms produce metabolites that inhibit angiogenesis. Procedures Fungal cultures were obtained from cases of keratomycosis, grown in Sabouraud's dextrose broth, and sterile filtered for use in experiments. The Matrigel assay was used to screen the filtrate samples for antiangiogenic activity. Matrigel is a basement membrane matrix that supports the differentiation of human umbilical vein endothelial (HUVE) cells into a capillary-like network of tubules. HUVE cells were cultured using standard techniques and passaged at confluence, with all cells being used at passage 3-6. HUVE cells (40 000 cells) were pipetted into each well of a 24-well tissue-culture plate coated with Matrigel. An aliquot of fungal media filtrate was added to each well and the plates allowed to incubate for 18 h, at which time they were evaluated for tubule formation. RESULTS: Two fungal isolates showed inhibition of tubule formation. The addition of 100, 200 and 400 &mgr;L of the fungal media filtrate from the first isolate (Fusarium sp. 99A34574) produced a consistent and dose-dependent inhibition of tubule formation. The second isolate (Aspergillus sp. 271599) did not show inhibition of tubule formation with 100 or 200 &mgr;L added to the wells, however, it did show inhibition at 400 &mgr;L/well. The remaining three isolates did not cause inhibition at any concentration. CONCLUSIONS: Our findings suggest that certain fungal organisms produce metabolites that inhibit tubule formation in vitro, and that these metabolites may play a significant role in altering the host vascular response to fungal infections of the cornea