An eight cytokine signature identified from peripheral blood serves as a fingerprint for hepatocellular cancer diagnosis

Background: Hepatocellular carcinoma is an aggressive disease in Asia and Africa with poor prognosis partially due to lack of disease-specific biomarkers.Objectives: The aim of this study was to assess the concentrations of different cytokines and chemokines in peripheral blood of patients with hepatocellular carcinoma and identify the potential biomarkers that would help in clinical assessment.Methods: Profiling of 14 cytokines, chemokines and growth factors was performed in peripheral blood of 78 patients and 78 healthy controls using Bio-Plex Human 15-plex assay kit.Results: The results showed that patients had significantly higher levels of IL-1β (p=0.034), IL-6 (p=2.13e-06),IL-10 (p=0.013), IL-17A (p=0.017), IL-22 (p=0.00276), IL-25 (p=0.0005), but lower levels of IL-4 (p=0.00341) and IL-33 (p=0.00982) in peripheral blood.Conclusion: We identified a unique eight-peripheral blood cytokines signature for hepatocellular carcinoma detection. This work will serve as the basis for further studies about the clinical value of peripheral blood cytokines in forecasting prognosisKeywords: Cytokine, peripheral blood, hepatocellular carcinoma, biomarker, diagnosis

An eight cytokine signature identified from peripheral blood serves as a fingerprint for hepatocellular cancer diagnosis

Background: Hepatocellular carcinoma is an aggressive disease in Asia and Africa with poor prognosis partially due to lack of disease-specific biomarkers. Objectives: The aim of this study was to assess the concentrations of different cytokines and chemokines in peripheral blood of patients with hepatocellular carcinoma and identify the potential biomarkers that would help in clinical assessment. Methods: Profiling of 14 cytokines, chemokines and growth factors was performed in peripheral blood of 78 patients and 78 healthy controls using Bio-Plex Human 15-plex assay kit. Results: The results showed that patients had significantly higher levels of IL-1\u3b2 (p=0.034), IL-6 (p=2.13e-06),IL-10 (p=0.013), IL-17A (p=0.017), IL-22 (p=0.00276), IL-25 (p=0.0005), but lower levels of IL-4 (p=0.00341) and IL-33 (p=0.00982) in peripheral blood. Conclusion: We identified a unique eight-peripheral blood cytokines signature for hepatocellular carcinoma detection. This work will serve as the basis for further studies about the clinical value of peripheral blood cytokines in forecasting prognosi

γ-Secretase Functions through Notch Signaling to Maintain Skin Appendages but Is Not Required for Their Patterning or Initial Morphogenesis

AbstractThe role of Notch signaling during skin development was analyzed using Msx2-Cre to create mosaic loss-of-function alleles with precise temporal and spatial resolution. We find that γ-secretase is not involved in skin patterning or cell fate acquisition within the hair follicle. In its absence, however, inner root sheath cells fail to maintain their fates and by the end of the first growth phase, the epidermal differentiation program is activated in outer root sheath cells. This results in complete conversion of hair follicles to epidermal cysts that bears a striking resemblance to Nevus Comedonicus. Sebaceous glands also fail to form in γ-secretase-deficient mice. Importantly, mice with compound loss of Notch genes in their skin phenocopy loss of γ-secretase in all three lineages, demonstrating that Notch proteolysis accounts for the major signaling function of this enzyme in this organ and that both autonomous and nonautonomous Notch-dependent signals are involved

N,N′-[(1S,2S)-Cyclo­hexane-1,2-di­yl]bis­(4-methyl­benzene­sulfonamide)

In the title compound, C20H26N2O4S2, the cyclo­hexane ring has a chair conformation. The two chiral C atoms are in S configurations. In the crystal, inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into chains propagating in [001]. Weak inter­molecular C—H⋯O hydrogen bonds further stabilize the crystal packing

An Algorithm for Identifying Novel Targets of Transcription Factor Families: Application to Hypoxia-inducible Factor 1 Targets

Efficient and effective analysis of the growing genomic databases requires the development of adequate computational tools. We introduce a fast method based on the suffix tree data structure for predicting novel targets of hypoxia-inducible factor 1 (HIF-1) from huge genome databases. The suffix tree data structure has two powerful applications here: one is to extract unknown patterns from multiple strings/sequences in linear time; the other is to search multiple strings/sequences using multiple patterns in linear time. Using 15 known HIF-1 target gene sequences as a training set, we extracted 105 common patterns that all occur in the 15 training genes using suffix trees. Using these 105 common patterns along with known subsequences surrounding HIF-1 binding sites from the literature, the algorithm searches a genome database that contains 2,078,786 DNA sequences. It reported 258 potentially novel HIF-1 targets including 25 known HIF-1 targets. Based on microarray studies from the literature, 17 putative genes were confirmed to be upregulated by HIF-1 or hypoxia inside these 258 genes. We further studied one of the potential targets, COX-2, in the biological lab; and showed that it was a biologically relevant HIF-1 target. These results demonstrate that our methodology is an effective computational approach for identifying novel HIF-1 targets

Clinical and Prognostic Value of PET/CT Imaging with Combination of 68

Background. To evaluate the clinical and prognostic value of PET/CT with combination of 68Ga-DOTATATE and 18F-FDG in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Method. 83 patients of GEP-NENs who underwent 68Ga-DOTATATE and 18F-FDG PET/CT were enrolled between June 2013 and December 2016. Well-differentiated (WD) NETs are divided into group A (Ki-67 < 10%) and group B (Ki-67 ≥ 10%), and poorly differentiated (PD) NECs are defined as group C. The relationship between PET/CT results and clinicopathological characteristics was retrospectively investigated. Result. For groups A/B/C, the sensitivities of 68Ga-DOTATATE and 18F-FDG were 78.8%/83.3%/37.5% and 52.0%/72.2%/100.0%. A negative correlation between Ki-67 and SUVmax of 68Ga-DOTATATE (R = −0.415; P ≤ 0.001) was observed, while a positive correlation was noted between Ki-67 and SUVmax of 18F-FDG (R = 0.683; P ≤ 0.001). 62.5% (5/8) of patients showed significantly more lesions in the bone if 68Ga-DOTATATE was used, and 22.7% (5/22) of patients showed more lymph node metastases if 18F-FDG was used. Conclusions. The sensitivity of dual tracers was correlated with cell differentiation, and a correlation between Ki-67 and both SUVmax of PET-CTs could be observed. 68Ga-DOTATATE is suggested for WD-NET and 18F-FDG is probably suitable for patients with Ki-67 ≥ 10%