Fibulin-3, originally identified in senescent and Werner syndrome fibroblasts, has been implicated in cell morphology, growth, adhesion and motility. Fibulin-3 exhibits both antitumor and oncogenic ...activities towards human cancers; however, the role of Fibulin-3 in hepatocellular carcinoma (HCC) remains elusive. In this study, we showed that both the mRNA and protein levels of Fibulin-3 were remarkably downregulated in HCC cell lines and fresh tissues. Immunohistochemical data revealed that Fibulin-3 was decreased in tumorous tissues in 67.1% (171/255) of cases compared to the corresponding adjacent nontumorous tissues. The results of statistical analysis indicated that low Fibulin-3 expression, defined by the receiver operating characteristic curve (ROC), was significantly associated with tumor differentiation (P=0.008), clinical stage (P=0.014) and serum AFP levels (P<0.01). Furthermore, Kaplan-Meier and multivariate analysis suggested that Fibulin-3 is an independent negative prognostic indicator for both overall (P<0.001) and recurrence-free (P=0.036) survival. In addition, an in vitro study demonstrated that knockdown of Fibulin-3 by siRNA markedly increased cell viability and promoted cell invasion in HCC cells. Collectively, our data suggest that Fibulin-3 exhibits antitumor effects towards HCC and serves as a biomarker of unfavorable prognosis for this deadly disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The metastasis-associated in colon cancer 1 gene (MACC1) has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of ...MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC).
mRNA and protein levels of MACC1 expression in one normal liver epithelial cells THLE3 and 15 HCC cell lines were examined using reverse transcription-PCR and Western blot. MACC1 expression was also comparatively studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Immunohistochemistry was employed to analyze MACC1 expression in 308 clinicopathologically characterized HCC cases. Statistical analyses were applied to derive association between MACC1 expression scores and clinical staging as well as patient survival.
Levels of MACC1 mRNA and protein were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. Significant difference in MACC1 expression was found in patients of different TNM stages (P<0.001). Overall survival analysis showed that high MACC1 expression level correlated with lower survival rate (P = 0.001). Importantly, an inverse correlation between MACC1 level and patient survival remained significant in subjects with early-stage HCC or with normal serum AFP level.
MACC1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Esophageal squamous cell carcinoma (ESCC) is a common malignant cancer worldwide. Despite recent improvements in surgical techniques and adjuvant therapies, the prognosis of patients with advanced ...ESCC remains poor. Resistance to chemoradiotherapy (CRT) remains a major cause of treatment failure for advanced ESCC patients. Here, we report that NRIP3 (nuclear receptor interacting protein 3) promotes ESCC tumor cell growth and resistance to CRT in ESCC cells by increasing and binding to DDI1 (DNA-damage inducible 1 homolog 1) and RTF2 (homologous to Schizosaccharomyces pombe Rtf2), and accelerating the removal of RTF2, which is a key determinant for the ability of cells to manage replication stress. In addition, we found that NRIP3 could increase DDI1 expression via PPARα. The NRIP3-PPARα-DDI1-RTF2 axis represents a protective molecular pathway in ESCC cells that mediates resistance to replication stress signals induced by chemoradiotherapy. In addition, elevated NRIP3 is associated with the poor clinical outcome of ESCC patients receiving radiotherapy and/or cisplatin-based chemotherapy. Our study therefore reveals that NRIP3 is a prognostic factor in ESCC and could have some predictive value to select patients who benefit from CRT treatment. A common mechanism that protects ESCC tumor cells from DNA damage induced by CRT is also revealed in this study.
Liver cancer ranks in prevalence and mortality among top five cancers worldwide. Accumulating interests have been focused in developing new strategies for liver cancer treatment. We have previously ...showed that dihydroartemisinin (DHA) exhibited antitumor activity towards liver cancer. In this study, we demonstrated that histone deacetylase inhibitors (HDACi) significantly augmented the antineoplastic effect of DHA via increasing apoptosis in vitro and in vivo. Inhibition of ERK phosphorylation contributed to DHA-induced apoptosis, due to the fact that inhibitor of ERK phosphorylation (PD98059) increased DHA-induced apoptosis. Compared with DHA alone, the combined treatment with DHA and HDACi reduced mitochondria membrane potential, released cytochrome c into cytoplasm, increased p53 and Bak, decreased Mcl-1 and p-ERK, activated caspase 3 and PARP, and induced apoptotic cells. Furthermore, we showed that HDACi pretreatment facilitated DHA-induced apoptosis. In Hep G2-xenograft carrying nude mice, the intraperitoneal injection of DHA and SAHA resulted in significant inhibition of xenograft tumors. Results of TUNEL and H&E staining showed more apoptosis induced by combined treatment. Immunohistochemistry data revealed the activation of PARP, and the decrease of Ki-67, p-ERK and Mcl-1. Taken together, our data suggest that the combination of HDACi and DHA offers an antitumor effect on liver cancer, and this combination treatment should be considered as a promising strategy for chemotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A pathologically complete response (pCR) or near pCR to neoadjuvant chemoradiotherapy (NCRT) might imply a better prognosis in patients with esophageal cancer. The aim of the study is to identify ...clinical factors associated with a pCR or near pCR.
We retrospectively analyzed 40 patients with radical esophagectomy after NCRT for esophageal squamous cell carcinoma (ESCC) from January 2001 to December 2006 in Sun Yat-sen University Cancer Center. Clinical factors included age, gender, weight loss, dysphagia, drinking status, smoking status, tumor location, tumor length, tumor grade, cT status, cN status, the regimen of chemotherapy and the interval between NCRT and surgery as potential predictors for a pCR or near pCR. Logistic regression was used to estimate the independent factors for a pCR or near pCR.
After surgical resection, 22.5% of the patients obtained the pCR. Patients with pCR had a better prognosis than those with non-pCR. However, there was no statistically significantly difference between the two groups (P=0.124). We separated the patients into pCR or near pCR (good responders, GRs) and poor responders (PR) based on the histology. GR showed better overall survival (OS) than PR (P=0.014). Univariate analysis indicated that short tumor length, good tumor grade and never drinking were associated with GR to NCRT. Using logistic regression analysis, good tumor grade was the only independent factor for the GR to NCRT (P=0.021). Cox regression revealed that weight loss, drinking status and GR were independent factors in ESCC patients with radical esophagectomy after NCRT.
Our study indicated that good tumor grade were an independent significant factor for the GR to NCRT. Weight loss, drinking status and GR were independent factors in patients with radical esophagectomy after NCRT. GR may improve OS of ESCC patients receiving NCRT.
Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be ...challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.
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•MMRNet can automatically predict MMR/MSI status from gastric cancer H&E-stained WSIs•A mapping approach MMRMapping can efficiently interpret MMRNet•The interpretable method can aid the growth of young pathologists
Pathology; Diagnostics; Cancer; Machine learning
Whether the association between body size or shape and nasopharyngeal carcinoma (NPC) risk exists or varies by age‐specific body size indicators is unclear. In a population‐based case–control study ...conducted in Southern China between 2010 and 2014, self‐reported height, weight, and body shape at age 20 and 10 years before interview were collected from 2448 histopathologically confirmed NPC cases and 2534 population‐based controls. Body mass index (BMI) was categorized according to the World Health Organization guidelines for Asian populations: underweight (<18.5 kg/m2), normal weight (18.5‐22.9 kg/m2), overweight (23.0‐27.4 kg/m2), and obese (≥27.5 kg/m2). Multivariate odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression. Furthermore, restricted cubic spline analysis was employed to examine nonlinear effects of BMI and body shape as continuous covariates. Underweight vs normal weight at age 20 years was associated with a 22% decreased NPC risk (OR, 0.78; 95% CI, 0.67, 0.90), whereas obesity was not significantly associated with NPC risk. Associations with BMI 10 years before the interview were similar. Having the leanest body shape at age 20 years, compared with the mode was not significantly associated with NPC risk (OR, 0.85; 95% CI, 0.62, 1.16), but having a larger body shape was associated with an elevated risk (OR, 1.25; 95% CI, 1.03, 1.52). Increasing BMI revealed positive trends with NPC risk. Despite some indication of significant findings, evidence for a strong association between BMI or body shape and NPC risk is still limited.
Underweight vs normal weight at age 20 years was associated with a decreased NPC risk, and having a larger body shape vs normal body shape was associated with an elevated risk; Increasing BMI revealed positive trends with NPC risk.
Abstract This study aimed to investigate the expression pattern and prognostic value of friend leukemia virus integration 1 (FLI-1) in nasopharyngeal carcinoma (NPC). Immunohistochemistry (IHC) ...staining of FLI-1 was performed in specimens from 198 untreated NPC patients. Ninety-nine patients were randomly assigned to the training set to analyze the prognostic value of FLI-1 and other clinicopathological characteristics, while the others were assigned to the testing set for validation. Clinicopathological data were compared using the Pearson chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to test independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI). Cytoplasmic FLI-1 expression positively correlated with N stage, distant metastasis and death ( P < 0.05) and also predicted poorer overall survival (OS) ( P = 0.014), distant metastasis-free survival (DMFS) ( P = 0.010), progression-free survival (PFS) ( P = 0.031). In multivariate analysis, FLI-1 expression and clinical stage were both independent prognostic factors of poor OS and DMFS. Prognoses of patients in the training set, the testing set, and the entire set were clearly divided into four risk subgroups by supplementing FLI-1 with clinical stage. These results indicate that FLI-1 expression is an independent prognostic factor for NPC patients and suggest that supplementing FLI-1 with clinical stage could be helpful for more accurate risk definition.
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