Detection of Citrobacter koseri carrying beta-lactamase KPC-2 in a hospitalised patient, Greece, July 2011

Microbial Biotechnolog

Analysis of Prostate Cancer Tumor Microenvironment Identifies Reduced Stromal CD4 Effector T-cell Infiltration in Tumors with Pelvic Nodal Metastasis.

BACKGROUND: Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively. OBJECTIVE: To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis. DESIGN SETTING AND PARTICIPANTS: We applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN-) pelvic nodal metastases. Both intraepithelial and stromal infiltrations of immune cells and differentially expressed genes (mRNA and protein levels) were correlated with the nodal status. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The identified CD4 effector cell signature of nodal metastasis was validated in a comparable independent patient cohort of 184 informative cases. Patient outcome analysis and decision curve analysis were performed with the CD4 effector cell density-based signature. RESULTS AND LIMITATIONS: In the discovery cohort, both tumor epithelium and stroma from patients with nodal metastasis had significantly lower infiltration of multiple immune cell types, with stromal CD4 effector cells highlighted as the top candidate marker. Targeted gene expression analysis and confirmatory protein analysis revealed key alteration of extracellular matrix components in tumors with nodal metastasis. Of note, stromal CD4 immune cell density was a significant independent predictor of LN metastasis (odds ratio [OR] = 0.15, p = 0.004), and was further validated as a significant predictor of nodal metastasis in the validation cohort (OR = 0.26, p < 0.001). CONCLUSIONS: Decreased T-cell infiltrates in the primary tumor (particularly CD4 effector cells) are associated with a higher risk of LN metastasis. Future evaluation of CD4-based assays on prostate cancer diagnostic biopsy materials may improve selection of at-risk patients for the treatment of LN metastasis. PATIENT SUMMARY: In this report, we found that cancer showing evidence of cancer metastasis to the lymph nodes tends to have less immune cells present within the tumor. We conclude that the extent of immune cells present within a prostate tumor can help doctors determine the most appropriate treatment plan for individual patients

BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (Pten BRF1 ) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In Pten BRF1 tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis

Demographic, clinical, and pathological features of early onset pancreatic cancer patients.

BACKGROUND: Early onset pancreatic cancer (EOPC), i.e. pancreatic ductal adenocarcinoma (PDAC) occurring in patients below 50 years of age, is rare and there is limited information regarding risk factors, molecular basis and outcome. This study aimed to determine the demographic and clinicopathological features and survival figures for EOPC. METHODS: A retrospective analysis of patients treated at the Royal London Hospital for PDAC between September 2004 and September 2015 was performed. Data on demographics, risk factors, presentation, pathological features, treatment and survival outcome were compared in EOPC and older PDAC patients. RESULTS: Of 369 PDAC cases identified, 35 (9.5%) were EOPC. Compared to older patients, EOPC patients were more frequently male (71% vs 54%, p = 0.043) and less commonly of British origin (37% vs 70%, p = 0.002). There was no significant difference regarding the prevalence of any of the risk factors known to be associated with older PDAC patients. Fewer EOPC patients presented with resectable disease (23% vs 44%, p = 0.015) and more received adjuvant chemo/radiotherapy (60% vs 46%, p = 0.008). The overall median survival and stage specific survival did not differ significantly between the two groups, although a longer survival for localized disease was seen in EOPC patients (25 months (12.9-37, 95%CI) vs 13 months (10.5-15.5 95%CI) for older PDAC patients). CONCLUSIONS: The EOPC patients had different demographics and were more likely than their older PDAC counterparts to be male. Typically they presented with more advanced disease, received more aggressive treatment, and had on overall similar survival outcome

Effect of immersion cleansing in color stability and hardness of soft denture reliners

Hygienic care of removable prostheses is important, and denture cleansers selected must be efficient and maintain the physicomechanical properties of soft reliners. Microwave energy has been reported to increase the sanitation effectiveness of denture cleansers. The purpose of the study was to evaluate hardness and color stability of some visible light polymerized and autopolymerized soft reliners after exposure in different denture-cleansing treatments. Six soft denture reliners (2 autopolymerized silicones, 1 autopolymerized acrylic, and 3 visible light polymerized ones) were exposed to 4 cleansing treatments (Corega Whitening, Polident 5-Minute, Corega Whitening + microwaving, Polident 5-Minute + microwaving). Hardness was measured with a Shore A durometer, and color changes were evaluated by a tristimulus colorimeter. The results were subjected to 2-way analysis of variance and Scheffé test for post hoc comparisons at a confidence level of α = 0.05. Sofreliner showed the smallest hardness change, and LightLiner the greatest. Versasoft and Sofreliner seem to have the lowest color change for every cleansing treatment examined, whereas LightLiner and Eversoft presented the greatest. Silicone-based materials demonstrated the smallest changes in both hardness and color, either when using water or with any of the other cleansing treatments. Copyright © 2012 by Mutaz B. Habal, MD

The effect of immersion cleansers on gloss, colour and sorption of acetal denture base material

The effect of immersion cleansers on gloss, colour and sorption of acetal denture base material Objective: To study the effect of peroxide and hypochlorite cleansers on gloss, colour and sorption of acetal denture resins. Materials and methods: Pink acetal and thermoplastic acrylic resins were evaluated. Thirty-five specimens 39 × 39 × 1.8 mm of each resin were prepared. Each group of specimens (n = 7) was then immersed into cleansers for 100 days. Group I immersed in tap water, Group II in Corega Extradent for 5 min, Group III in Corega Extradent for 8 h, Group IV in NitrAdine™ Seniors for 15 min and Group V in NaOCl 5.25%. Gloss, colour and weight measurements were taken initially and after 100 days. Data subjected to two-way anova and Tukey&apos;s test at α = 0.05. Results: Acrylic resin showed reductions of glossiness from -5 to -15 and acetal from -0.2 to -6. Colour changes (δ E*) ranged from 2.64 to 7.64 for acrylic and 2.77 to 26.54 for acetal resin. Sorption for acrylic ranged from 11.64 to 17.06 μg/mm3 and 9.18 to 24.79 μg/mm3 for acetal resin. The results of (δ E*) and sorption showed an interaction between denture resins and cleansers. Conclusions: The gloss of acetal resin was less affected by water, peroxides and NaOCl 5.25% compared with acrylic resin. Acetal resin showed clinically acceptable (δ E*) whereas acrylic resin unacceptable ones for water and peroxide solutions. The immersion of acetal resin in NaOCl 5.25% showed clinically unacceptable (δ E*) and higher sorption and should be avoided or should be managed with care. © 2012 John Wiley &amp;amp; Sons A/S and The Gerodontology Society. Published by John Wiley &amp;amp; Sons Ltd

SLFN5 regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer

Androgen-deprivation therapy (ADT) is the standard of care for treatment of non-resectable prostate cancer (PCa). Despite high treatment efficiency, most patients ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we performed a comparative proteomic analysis of three in vivo, androgen receptor (AR)-responsive orthograft models of matched hormone-naive PCa and CRPC. Differential proteomic analysis revealed that distinct molecular mechanisms, including amino acid (AA) and fatty acid (FA) metabolism, are involved in the response to ADT in the different models. Despite this heterogeneity, Schlafen family member 5 (SLFN5) was identified as an AR-regulated protein in CRPC. SLFN5 expression was high in CRPC tumors and correlated with poor patient outcome. In vivo, SLFN5 depletion strongly impaired tumor growth in castrated conditions. Mechanistically, SLFN5 interacted with ATF4 and regulated the expression of LAT1, an essential AA transporter. Consequently, SLFN5 depletion in CRPC cells decreased intracellular levels of essential AA and impaired mTORC1 signalling in a LAT1-dependent manner. These results confirm that these orthograft models recapitulate the high degree of heterogeneity observed in CRPC patients and further highlight SLFN5 as a clinically relevant target for CRPC