The deletion of 16q23-q24 belongs to the most frequent chromosomal changes in prostate cancer, but the clinical consequences of this alteration have not been studied in detail. We performed fluorescence in situ hybridization analysis using a 16q23 probe in more than 7,400 prostate cancers with clinical follow-up data assembled in a tissue microarray format. Chromosome 16q deletion was found in 21% of cancers, and was linked to advanced tumor stage, high Gleason grade, accelerated cell proliferation, the presence of lymph node metastases (p < 0.0001 each) and positive surgical margin (p 5 0.0004). 16q Deletion was more frequent in ERG fusion-positive (27%) as compared to ERG fusion-negative cancers (16%, p < 0.0001), and was linked to other ERG-associated deletions including phosphatase and tensin homolog (PTEN) (p < 0.0001) and 3p13 (p 5 0.0303). In univariate analysis, the deletion of 16q was linked to early biochemical recurrence independently from the ERG status (p < 0.0001). Tumors with codeletions of 16q and PTEN had a worse prognosis (p 5 0.0199) than those with PTEN or the deletion of 16q alone. Multivariate modeling revealed that the prognostic value of 16q/PTEN deletion patterns was independent from the established prognostic factors. In summary, the results of our study demonstrate that the deletion of 16q and PTEN cooperatively drives prostate cancer progression, and suggests that deletion analysis of 16q and PTEN could be of important clinical value particularly for preoperative risk assessment of the clinically most challenging group of low-and intermediated grade prostate cancers.Prostate cancer is the most frequent malignancy in men. The clinical behavior ranges from slowly growing indolent tumors to highly aggressive and metastatic cancers. Based on the results of large autopsy studies-demonstrating a high prevalence of prostate cancers also in men who never experienced symptoms of the disease during their life time-it is estimated that a significant fraction of prostate cancer patients may be manageable without surgery and its associated severe side effects.1 It is hoped that a better understanding of the molecular features underlying prostate cancer development and progression will substantially improve the prediction of the clinical course of prostate cancer patients.Chromosomal rearrangements are a major mechanism for activating and inactivating oncogenes and tumor suppressor genes in cancer. In contrast to most other cancers, chromosomal rearrangements mostly involve translocations and deletions but only rarely copy number gains or amplifications in prostate cancer. With the exception of the TMPRSS2:ERG fusion occurring in subpopulations of most prostate cancers, individual translocations generally occur at very low frequency (<5%).2 Many chromosomal deletions, however, are highly recurrent and occur at frequencies >10% of cancers, including 8p (40-50%), 13q14, 16q22-q24, 6q12-q22, 10q23 (20-30% each), 12p12-p13, 3p13 (15-20% each) and 5q21 (10%).3-9 The exact biological mechanism of how the...

Prostate cancer is characterized by recurrent deletions that can considerably vary in size. We hypothesized that large deletions develop from small deletions and that this “deletion lengthening” might have a “per se” carcinogenic role through a combinatorial effect of multiple down regulated genes. In vitro knockdown of 37 genes located inside the 6q12-q22 deletion region identified 4 genes with additive tumor suppressive effects, further supporting a role of the deletion size for cancer aggressiveness. Employing fluorescence in-situ hybridization analysis on prostate cancer tissue microarrays, we determined the deletion size at 6q and 16q in more than 3,000 tumors. 16q and 6q deletion length was strongly linked to poor clinical outcome and this effect was even stronger if the length of both deletions was combined. To study deletion lengthening in cancer progression we eventually analyzed the entire cancers from 317 patients for 6q and 16q deletion length heterogeneity and found that the deletion expanded within 50-60% of 6q and 16q deleted cancers. Taken together, these data suggest continuous “deletion lengthening” as a key mechanism for prostate cancer progression leading to parallel down regulation of genes with tumor suppressive properties, some of which act cooperatively.

<b><i>Background:</i></b> To date, there are inconsistent data about relationships between diffusion-weighted imaging (DWI) and tumor grading/microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Our purpose was to systematize the reported results regarding the role of DWI in prediction of tumor grading/MVI in HCC. <b><i>Method:</i></b> MEDLINE library, Scopus, and Embase data bases were screened up to December 2019. Overall, 29 studies with 2,715 tumors were included into the analysis. There were 20 studies regarding DWI and tumor grading, 8 studies about DWI and MVI, and 1 study investigated DWI, tumor grading, and MVI in HCC. <b><i>Results:</i></b> In 21 studies (1,799 tumors), mean apparent diffusion coefficient (ADC) values (ADC_mean) were used for distinguishing HCCs. ADC_mean of G1–3 lesions overlapped significantly. In 4 studies (461 lesions), minimum ADC (ADC_min) was used. ADC_min values in G1/2 lesions were over 0.80 × 10⁻³ mm²/s and in G3 tumors below 0.80 × 10⁻³ mm²/s. In 4 studies (241 tumors), true diffusion (<i>D</i>) was reported. A significant overlapping of <i>D</i> values between G1, G2, and G3 groups was found. ADC_mean and MVI were analyzed in 9 studies (1,059 HCCs). ADC_mean values of MIV+/MVI− lesions overlapped significantly. ADC_min was used in 4 studies (672 lesions). ADC_min values of MVI+ tumors were in the area under 1.00 × 10⁻³ mm²/s. In 3 studies (227 tumors), <i>D</i> was used. Also, <i>D</i> values of MVI+ lesions were predominantly in the area under 1.00 × 10⁻³ mm²/s. <b><i>Conclusion:</i></b> ADC_min reflects tumor grading, and ADC_min and <i>D</i> predict MVI in HCC. Therefore, these DWI parameters should be estimated for every HCC lesion for pretreatment tumor stratification. ADC_mean cannot predict tumor grading/MVI in HCC.

Traumatic brain injury (TBI) may cause damage to distant organs. Acute ethanol intoxication (EI) induces complex local and systemic anti-inflammatory effects and influences the early outcomes of traumatized patients. Here, we evaluated its effects on the BI-induced expression of local inflammatory mediators in the trauma-remote organs the lungs and liver. Male mice were exposed to ethanol as a single oral dose (5g·kg–1, 32%) before inducing a moderate blunt TBI. Sham groups underwent the same procedures without TBI. Ether 3 or 6h after the TBI, the lung and liver were collected. The gene expression of HMGB1, IL-6, MMP9, IL-1β, and TNF as well as the homogenate protein levels of receptor for advanced glycation end products (RAGE), IL-6, IL-1β, and IL-10 were analyzed. Liver samples were immunohistologically stained for HMGB1. EI decreased the gene expressions of the proinflammatory markers HMGB1, IL-6, and MMP9 in the liver upon TBI. In line with the reduced gene expression, the TBI-induced protein expression of IL-6 in liver tissue homogenates was significantly reduced by EI at 3h after TBI. While the histological HMGB1 expression was enhanced by TBI, the RAGE protein expression in the liver tissue homogenates was diminished after TBI. EI reduced the histological HMGB1 expression and enhanced the hepatic RAGE protein expression at 6h post TBI. With regard to the lungs, EI significantly reduced the gene expressions of HMGB1, IL-6, IL-1β, and TNF upon TBI, without significantly affecting the protein expression levels of inflammatory markers (RAGE, IL-6, IL-1β, and IL-10). At the early stage of TBI-induced inflammation, the gene expression of inflammatory mediators in both the lungs and liver is susceptible to ethanol-induced remote effects. Taken together, EI may alleviate the TBI-induced pro-inflammatory response in the trauma-distant organs, the lungs and liver, via the HMGB1-RAGE axis.

No abstract

No abstract

Background/Aim: The effect of sarcopenia on patients with severe Covid-19 disease is unknown. We aimed to assess the influence of baseline computed tomography (CT)-based body composition parameters (pectoralis muscle area, pectoralis muscle index, skeletal muscle gauge) on clinical variables in patients with severe Covid-19 disease. Patients and Methods: Chest CT scans of adult patients with confirmed Covid-19 who were hospitalized from March 2020 to May 2021 at a level-one medical center in Germany were retrospectively analyzed. Pectoralis muscle area, pectoralis muscle index and skeletal muscle gauge were measured on the first CT scan after admission. Body composition parameters were assessed for association with clinical variables and 30day mortality. Results: A total of 46 patients were included. None of the body composition parameters was a predictor for 30-day mortality, duration of hospital stay, duration of intensive care unit treatment, or duration of invasive mechanical ventilation. Conclusion: Pectoralis muscle composition parameters in CT chest scans did not predict outcomes in adult patients with severe Covid-19 infection.Sarcopenia is an abnormal body composition defined as the loss of muscle mass, low muscle strength, and impaired muscle quality (1). Screening measures include clinical parameters as well as image-based techniques (1, 2). Sarcopenia is common in patients aged 65 years and older and has been related to worse clinical outcome, disability, This article is freely accessible online.

No abstract