Is periprostatic adipose tissue associated with aggressive tumor biology in prostate cancer?

The prevalence of overweight and obesity and their health-related problems have been increasing.Obesity is increasingly recognized as a risk factor in different types of cancer in humans.The mechanisms supporting the link between obesity and cancer development have not been fully understood.Leptin,a circulating cytokine produced by adipocytes,may influence prostate cancer(PCa)progression in different ways.Body mass index seems to be an unreliable predictor for the development of PCa,but its influence on progression and poor oncological outcomes seems to be clear.Given the fact that abdominal fat is the most metabolically active fat,with different metabolic and paracrine effects,related anthropometric measurements may lead to a better estimation of PCa risk.Metabolically active periprostatic abdominal fat may also play an important role in releasing cytokines and growth factors that may promote tumor cell proliferation or even create a favorable environment for aggressive tumor biology.Different imaging measurements,e.g.,periprostatic adipose tissue(PPAT)thickness,may be significant predictors of PCa.Several genes in the PPAT of obese men have been identified to contribute to chronic immuno-inflammatory responses which eventually lead to cell cycle alterationwith oncological potential.In vitro studies showed the importance of PCa and its interaction with its microenvironment particularly in patients with aggressive PCa.Different types of cytokines,such as interleukin-6,may promote a tumorigenic microenvironment.This article endeavors to review the current literature on the association of PPAT with aggressive tumor biology in PCa.     

Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight ‘anomalous’ cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first ‘anomalous’ non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

In vivo inhibition of oxidative drug metabolism by, and acute toxicity of, 1-aminobenzotriazole (ABT). A tool for biochemical toxicology

One hour following intravenous pretreatment of rats with 50 mg/kg of the cytochrome P-450 suicide substrate 1-aminobenzotriazole (ABT), the metabolism of phenacetin to acetaminophen is inhibited completely [B. A. Mico et al., Drug Metab. Dispos. 15, 274 (1987)]. Here we report an examination of the time-course of inhibition of phenacetin elimination by ABT, a demonstration of dose-dependent inhibition of phenacetin and antipyrine clearances by ABT, and an examination of the acute toxicity of ABT in rats, as well as the effect of ABT on phenacetin metabolism in beagles. After a 1-, 12-, 24- or 36-hr pretreatment of rats with ABT (50 mg/kg, i.v.), the clearance of phenacetin was decreased 85, 88, 81 and 48%, respectively, from control values. Twelve hours after intraperitoneal pretreatment of rats with 0.3, 1.0, 5.0, 20, and 50 mg/kg of ABT, the total systemic clearance of phenacetin was suppressed 39, 47, 60, 75, and 79%, respectively, from control values. The clearance of intravenously administered antipyrine was decreased 38 and 66% after a 12-hr intraperitoneal pretreatment of rats with 10 or 50 mg/kg of ABT. In rats, no hematological, clinical chemistry, macroscopic, or microscopic abnormalities were detected 1, 2, 3, and 9 days after a single i.v. dose of ABT (50 mg/kg). A 1-hr pretreatment of beagles with ABT (20 mg/kg) decreased the clearance of intravenous phenacetin 50% and completely prevented the formation of acetaminophen. These results demonstrate that ABT pretreatment causes long-lasting inhibition of oxidative drug metabolism without disruption of normal physiological processes. Profound inhibition of oxidation in two species suggests that ABT may have general utility as an inhibitor of oxidative drug metabolism in biochemical pharmacology and toxicology studies.     

Complications of automatic implantable cardioverter defibrillators: radiographic, CT, and echocardiographic evaluation

Automatic implantable cardioverter defibrillators (AICDs) were studied in three groups: (a) Serial radiographs were reviewed in 51 clinic patients. Twenty of 96 (21%) AICD patches distorted with time. (b) Thirty-six postoperative computed tomographic (CT) scans of asymptomatic patients revealed that pericardial fluid collections were frequent during the month after surgery but rare beyond that. Echocardiography was insensitive for these collections. CT also demonstrated dense fibrosis around some distorted patches, months after surgery. (c) Five other patients with pericardial infection had distorted patches, and the four studied with CT had fluid beneath their patches. (d) A case of constrictive pericarditis had distorted patches but was not diagnosed with CT. The authors conclude that distorted patches may indicate postoperative complications and that CT is the imaging modality of choice.     

Chest radiography: a survey of techniques and exposure levels currently used

In diagnostic radiology, the routine measurement of exposure levels for a reference patient is an important part of an effective quality assurance program. In the United States, chest radiography is the most frequent examination and has the lowest exposure level of all radiologic examinations. We estimated the amount of exposure an average patient received from both manual and automatic exposure-controlled radiographic techniques by using a "patient-equivalent" chest phantom during measurements. A densitometric procedure was used to assess processor performance. The mean exposure from 194 chest systems was 20 mR (5.16 X 10(-5) C/kg); the mean film density, 1.38; and the mean processing speed, 108. It is interesting to note that a wide range of radiographic techniques, processing conditions, and screen-film speeds are currently being used. With the information given in our study, investigators can begin to identify the problems that lead to unusual exposure levels and, perhaps, poor image quality.     

丹酚酸A对小鼠脑缺血再灌注致学习记忆功能障碍的改善作用及作用机制

本实验采用脑缺血再灌注损伤造成小鼠学习记忆功能障碍模型。通过跳台和避暗实验法研究了丹酚酸对记忆获得功能障碍的改善作用。结果表明丹酚酸Ａ３，１０ｍｇ·ｋｇ－１ｉｖ可以减轻脑缺血再灌注导致的小鼠学习记忆功能障碍状态。并使小鼠脑缺血再灌注后脑组织中脂质过氧化产物ＭＤＡ含量明显降低。体外实验表明丹酚酸Ａ１０－８～１０－７’ｍｏｌ·Ｌ－１可以抑制大鼠脑组织匀浆脂质过氧化反应和羟自由基（·ＯＨ）的生成，表现出较强的抗氧化作用，提示丹酚酸改善脑缺血再灌注损伤的主要机制可能与其抗氧化作用有关。