Κυριακή 3 Νοεμβρίου 2019

Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients

Abstract

Background and Aims

Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients.

Methods

A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population.

Results

Of the 27 digitized features at the 12th thoracic vertebral level, six features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) were able to stratify patients into high- and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044, respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor.

Conclusion

Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.

It’s What’s Up Front That Counts—Part Two: Esophageal Crohn’s Disease Complicated by Recurrent Upper Gastrointestinal Bleeding

Liver Transplantation for Acetaminophen-Induced Acute Liver Failure: Role of Psychiatric Comorbidity in Listing Decisions and Outcomes

Abstract

Background

Psychiatric co-morbidities are thought to deter listing of patients with acetaminophen-induced acute liver failure (APAP-ALF) for liver transplantation (LT). We examined the listing process and short-term outcomes via a cohort study of APAP-ALF patients with and without psychiatric comorbidity.

Methods

We analyzed listing determinants, listing rates, and short-term (21-day) outcomes in APAP-ALF patients with and without psychiatric comorbidity (mental illness and/or substance abuse) enrolled in the ALFSG registry between 2000 and 2016.

Results

Of the 910 APAP-ALF patients, 801 (88%) had evidence of psychiatric comorbidity. There was no difference in listing between patients with (169/801, 21%) and without (26/109, 24%) psychiatric comorbidity (p = 0.59). Listed patients in both groups were younger with more severe admission clinical parameters than those not listed. Patients with and without psychiatric comorbidity had similar short-term outcomes: transplant rates among listed patients [57/169 (34%) vs 10/26 (39%), p = 0.80], spontaneous (transplant-free) survival (SS) [544/801 (68%) vs 73/109 (67%), p = 0.93], and overall death [207/801 (26%) vs 26/109 (24%), p = 0.74].

Conclusions

In our study, which is limited by informal psychiatric assessments, psychiatric comorbidity in APAP-ALF patients does not appear to impact listing, or short-term outcomes—SS, LT, or death. Transplant listing decisions primarily appear to be based on clinical severity of disease, rather than concern that APAP-ALF patients’ psychiatric comorbidity will compromise outcomes.

MiR-525-5p Repressed Metastasis and Anoikis Resistance in Cervical Cancer via Blocking UBE2C/ZEB1/2 Signal Axis

Abstract

Background

Accumulating evidence indicated that miRNAs are important regulators involved in cancer biology.

Aims

We aimed to investigate the biological functions and potentially underlying molecular mechanism of miR-525-5p in CC.

Methods

RT-PCR and Western blot assay were performed to detect mRNA and protein expression. Cell proliferation, anoikis resistance, and cell invasion were analyzed.

Results

We observed that the expression of miR-525-5p was declined in several CC cell lines. Additionally, introduction of miR-525-5p dramatically hampered cell viability, invasiveness, and migration ability through modulating epithelial-to-mesenchymal transition (EMT) marked genes as reflected by the upregulation of E-cadherin, as well as the downregulation of vimentin and N-cadherin. Furthermore, administration of miR-525-5p markedly reduced anchorage-independent growth and anoikis resistance accompanied by a decrease in the expression of anti-apoptotic protein Bcl-2 and an increase in the expression of pro-apoptotic protein Bax, C-caspase 3, and C-PARP1. Most importantly, analysis using publicly available algorithms predicted that UBE2C was a direct and functional target of miR-525-5p. Luciferase assays coupled with RT-PCR and Western blot analysis further verified that miR-525-5p negatively regulated UBE2C expression. Interestingly, miR-525-5p modulated ZEB1/2 expression via targeting UBE2C. Mechanically, administration of UBE2C partially blunted the salutary effects of miR-525-5p on invasive ability, EMT, and anoikis resistance, indicating that miR-525-5p acts as a tumor suppressor in CC largely through repression of UBE2C/ZEB1/2 signaling.

Conclusions

Taken together, our data identify a novel signaling axis of miR-525-5p/UBE2C/ZEB1/2 in repressing EMT and anoikis resistance, and likely serve as a potential therapeutic target for CC metastasis and prognosis as well as a therapeutic application.

Retraction Note to: Effect of miR-451 on the Biological Behavior of the Esophageal Carcinoma Cell Line EC9706
The Editor-in-Chief has retracted this article [1] because Figure 8 overlaps with Figure 6b of [2] and Figure 6 overlaps with Figure 3 of [3] and Figure 3 of [4].

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