Gastric carcinoma showing an abrupt transition from a tubular to solid pattern is an unusual phenomenon reminiscent of dedifferentiation. The phenotypic and molecular characteristics of this ...transition are still unclear. We retrospectively collected 41 gastric carcinomas exhibiting dedifferentiation-like tubular to solid transition and applied an array of immunohistochemical stains, including neuroendocrine and hepatocytic markers, to delineate their lineage. The status of Epstein-Barr virus (EBV) infections, mismatch repair proteins, SWI/SNF complex proteins and p53 expression levels were examined. The clinicopathologic differences were assessed by statistical analysis. Except for 10 cases with neuroendocrine differentiation and 2 EBV-associated carcinomas, we identified 8 hepatoid carcinomas and 21 solid adenocarcinomas with loss of CDX2 and/or hep-par1 expression in solid part (12/29). A subset of solid adenocarcinoma was associated with MSI (8) and mutant p53 expression was frequent in non-MSI cases (10/13). We found hepatoid carcinomas usually harbored SMARCA2 loss (5/8), MSI-associated cases commonly had ARID1A loss (6/8), and non-MSI solid adenocarcinomas frequently showed SMARCA2/A4 loss (7/13) with a high rate of concurrent ARID1A loss (4/7). Spatial correlation between solid transition and loss of SWI/SNF complex subunits were seen in 63% of tumors (12/19). Dedifferentiation-like tubular and solid carcinoma was associated with a propensity to inferior survival outcomes (
p
= 0.034), especially hepatoid carcinoma and in the non-MSI/EBV intestinal subgroup. In conclusion, gastric cancer exhibiting dedifferentiation-like tubular to solid transition is a phenotypically divergent group that shares common alterations in the SWI/SNF complex.
Although men carry a higher risk of hepatocellular carcinoma (HCC) than women, it is still controversial whether men also have a poorer postoperative prognosis. A retrospective study was conducted to ...evaluate the postoperative prognostic predictors of HCC focusing on sex differences.
We enrolled 516 consecutive adult patients with HCC (118 women, 398 men), who received surgical resection between January 2000 and December 2007, and were followed-up for >10 years. Clinical and laboratory data together with postoperative outcomes were reviewed.
At baseline, female patients had a higher anti-hepatitis C virus antibody prevalence (P = 0.002); lower hepatitis B virus surface antigen prevalence (P = 0.006); less microvascular invasion (P = 0.019); and lower alpha-fetoprotein (P = 0.023), bilirubin (P = 0.002), and alanine transaminase (P = 0.001) levels. Overall, there were no significant sex differences in terms of intrahepatic recurrence-free survival (RFS), distant metastasis-free survival (MFS), and overall survival (OS). However, subgroup analysis showed that women had favorable RFS (P = 0.019) and MFS (P = 0.034) in patients with alpha-fetoprotein ≤ 35 ng/mL, independent of other clinical variables (adjusted P = 0.008 and 0.043, respectively). Additionally, men had favorable OS in patients with prothrombin time (international normalized ratio INR) <1.1 (P = 0.033), independent of other clinical variables (adjusted P = 0.042).
Female sex is independently associated with favorable postoperative RFS and MFS in patients with alpha-fetoprotein ≤35 ng/mL, while male sex is independently associated with favorable OS in patients with prothrombin time INR <1.1.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Extracellular vesicles (EVs) are valuable sources for the discovery of useful cancer biomarkers. This study explores the potential usefulness of tumor cell-derived EV membrane proteins as plasma ...biomarkers for early detection of colorectal cancer (CRC). EVs were isolated from the culture supernatants of four CRC cell lines by ultracentrifugation, and their protein profiles were analyzed by LC-MS/MS. Bioinformatics analysis of identified proteins revealed 518 EV membrane proteins in common among at least three CRC cell lines. We next used accurate inclusion mass screening (AIMS) in parallel with iTRAQ-based quantitative proteomic analysis to highlight candidate proteins and validated their presence in pooled plasma-generated EVs from 30 healthy controls and 30 CRC patients. From these, we chose 14 potential EV-derived targets for further quantification by targeted MS assay in a separate individual cohort comprising of 73 CRC and 80 healthy subjects. Quantitative analyses revealed significant increases in ADAM10, CD59 and TSPAN9 levels (2.19- to 5.26-fold, p < 0.0001) in plasma EVs from CRC patients, with AUC values of 0.83, 0.95 and 0.87, respectively. Higher EV CD59 levels were significantly correlated with distant metastasis (p = 0.0475), and higher EV TSPAN9 levels were significantly associated with lymph node metastasis (p = 0.0011), distant metastasis at diagnosis (p = 0.0104) and higher TNM stage (p = 0.0065). A two-marker panel consisting of CD59 and TSPAN9 outperformed the conventional marker CEA in discriminating CRC and stage I/II CRC patients from healthy controls, with AUC values of 0.98 and 0.99, respectively. Our results identify EV membrane proteins in common among CRC cell lines and altered plasma EV protein profiles in CRC patients and suggest plasma EV CD59 and TSPAN9 as a novel biomarker panel for detecting early-stage CRC.
Background
In the 8th edition of American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC), tumor size is not considered in T1 stage. The present study aimed to find ...out the optimal cutoff for tumor size to further stratify patients with T1 HCC.
Methods
Operated HCC patients were identified from the Chang Gung Research Database (CGRD), and the patients with T1bN0M0 tumors were further divided into two groups based on the tumor size. The resulting subgroups were denoted as T1b (≤ cutoff) and T1c (> cutoff). The survivals were compared between T1a/b and T1c as well as T1c and T2.
Results
From 2002 to 2018, a total of 2893 patients who underwent surgery for T1N0M0 HCC were identified from the CGRD. After excluding cases who died within 30 days of surgery, Kaplan–Meier survival analysis discovered that T1 tumors > 65 mm (T1c) had survivals similar to those of T2N0M0 tumors. Cox regression multivariate analysis further demonstrated that tumor size > 6.5 cm was an independent poor prognostic indicator for T1 HCC. Sensitivity tests also confirmed that tumors lager than 6.5 cm were significantly more likely to develop both tumor recurrence and liver-specific death after surgery.
Conclusions
Our study demonstrated that tumor size would significantly impact the survival outcome of T1 HCC after surgery. Due to significantly worse survival, we proposed a subclassification within T1 HCC, T1c: solitary tumor > 6.5 cm without vascular invasion, to further stratify those patients at risk. Further studies are mandatory to validate our findings.
Lindley var.
Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of ...endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using an in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286), and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration, and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor), and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (an NOS inhibitor). Moreover, chronic treatment with TCEE attenuated hyperlipidemia, systemic and aortic inflammatory response, and the atherosclerotic lesions in apolipoprotein E-deficient mice. Collectively, our findings suggest that TCEE may confer protection from atherosclerosis by preventing endothelial dysfunction.
To explore the correlation of metabolomics profiles of gastric cancer (GC) with its chromosomal instability (CIN) status.
Nineteen GC patients were classified as CIN and non-CIN type by The Cancer ...Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatography-mass spectrometry. Groups were compared by defining variable importance in projection score of > 1.2, a fold change value or its reciprocal of > 1.2, and a
value of < 0.05 as a significant difference.
In total, twelve men and seven women were enrolled, with a median age of 66 years (range, 47-87 years). The numbers of gene alterations in the CIN GC group were significantly higher than those in the non-CIN GC (32-218
2-17;
< 0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated significantly higher aspartic acid, citicoline, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-N-acetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels (all
< 0.05). CIN tumors contained significantly higher phosphocholine and uridine 5'-monophosphate levels but significantly lower beta-citryl-L-glutamic acid levels than did non-CIN tumors (all
< 0.05). CIN GC tumors demonstrated additional altered pathways involving alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.
Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.
Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the postoperative prognostic value of the virological factors assayed directly from liver tissue has ...never been investigated. To address this issue, 185 liver samples obtained from the noncancerous part of surgically removed HBV‐associated HCC tissues were subjected to virological analysis. Assayed factors included the amount of HBV‐DNA in the liver tissues; genotype; and the presence of the HBV precore stop codon G1896A mutation, basal core promoter A1762T/G1764A mutation, and pre‐S deletions/stop codon mutation. All virological factors and clinicopathological factors were subjected to Cox proportional hazard model analysis to estimate postoperative survival. It was found that an HBV‐DNA level >3.0 × 107 copies/g of liver tissue and the presence of the basal core promoter mutation independently predicted disease‐free (adjusted hazard ratio 1.641 95% confidence interval (CI) 1.010‐2.667 and 2.075 95% CI 1.203‐3.579, respectively) and overall (adjusted hazard ratio 2.807 95% CI 1.000‐7.880 and 5.697 95% CI 1.678‐19.342, respectively) survival. Kaplan‐Meier survival analysis indicated that in‐frame, short stretch (<100 bp) pre‐S deletions, but not large fragment (>100 bp) pre‐S deletions, were significantly associated with poorer disease‐free (P = 0.005) and overall (P = 0.020) survival. A hot deletion region located between codons 107 and 141 of the pre‐S sequence was identified for the short stretch pre‐S deletion mutants. Conclusion: The amount of HBV‐DNA in liver tissue and the presence of the basal core promoter mutation were two independent predictors for postoperative survival in HCC. A short stretch pre‐S deletion located between codons 107 and 141 was strongly associated with a poorer postoperative prognosis. (Hepatology 2010)
Purpose:
Radiofrequency ablation (RFA) is a widely used alternative modality in the treatment of liver tumors. Ultrasound B-mode imaging is an important tool to guide the insertion of the RFA ...electrode into the tissue. However, it is difficult to visualize the ablation zone because RFA induces the shadow effect in a B-scan. Based on the randomness of ultrasonic backscattering, this study proposes ultrasound Nakagami imaging, which is a well-established method for backscattered statistics analysis, as an approach to complement the conventional B-scan for evaluating the ablation region.
Methods:
Porcine liver samples (n = 6) were ablated using a RFA system and monitored by employing an ultrasound scanner equipped with a 7.5 MHz linear array transducer. During the stages of ablation (0–12 min) and postablation (12–24 min), the raw backscattered data were acquired at a sampling rate of 30 MHz for B-mode, Nakagami imaging, and polynomial approximation of Nakagami imaging. The contrast-to-noise ratio (CNR) was also calculated to compare the image contrasts of the B-mode and Nakagami images.
Results:
The results demonstrated that the Nakagami image has the ability to visualize changes in the backscattered statistics in the ablation zone, including the shadow region during RFA. The average Nakagami parameter increased from 0.2 to 0.6 in the ablation stage, and then decreased to approximately 0.3 at the end of the postablation stage. Moreover, the CNR of the Nakagami image was threefold that of the B-mode image, showing that the Nakagami image has a better image contrast for monitoring RFA. Specifically, the use of the polynomial approximation equips the Nakagami image with an enhanced ability to estimate the range of the ablation region.
Conclusions:
This study demonstrated that ultrasound Nakagami imaging based on the analysis of backscattered statistics has the ability to visualize the RFA-induced ablation zone, even if the shadow effect exists in the B-scan.
Background
Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the ...curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction.
Aim
Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer.
Methods
Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue.
Results
Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all
P
values < 0.05).
Conclusions
Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.
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