BackgroundHypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are frequently overexpressed in numerous types of cancers and are known to be important regulators of angiogenesis. Until now, few studies have been carried out to investigate the prognostic role of these factors in solid tumors, especially in colorectal cancer (CRC). The purpose of this study was to evaluate the expression of HIF-1α and VEGF in CRC tissues, and to analyze the association of these two factors with several clinical and pathological characteristics, and patients' survival.MethodsParaffin-embedded tissue samples were retrospectively collected from 71 CRC patients, who received surgical resection between 2001 and 2002, with a median follow-up of 5 years. We examined the patterns of expression of HIF-1α and VEGF by immunohistochemistry method. Statistical analysis was performed with univariate tests and multivariate Cox proportional hazards model to evaluate the differences.ResultsExpression of HIF-1α and VEGF was positively observed in 54.93% and 56.34% among the patients, respectively. HIF-1α and VEGF status were significantly associated with tumor stage, lymph nodes and liver metastases (P < 0.05). Expression of both HIF-1α and VEGF remained significantly associated with overall survival (OS) (P < 0.01), and HIF-1α was positively correlative to VEGF in CRC (r = 0.72, P < 0.001).ConclusionsHIF-1α and VEGF could be used as biomarkers indicating tumors in advanced stage and independently implied poor prognosis in patients with CRC. Treatment that inhibits HIF-1α might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be.
The gastrointestinal tract is the most common extranodal invasion site of non-Hodgkin lymphoma (NHL). Primary gastrointestinal NHL is often discussed together in most survival analyses. Primary intestinal NHL is significantly different from primary gastric NHL with regard to clinical features, pathological subtype, treatment, and prognosis. In this article, we analyzed clinical and pathological characteristics of primary intestinal NHL, and we also explored prognostic factors for primary intestinal NHL. A retrospective analysis was carried out on clinical data from 116 cases of confirmed primary intestinal NHL. The Kaplan-Meier method was used for the survival analysis. A Cox model was used for a multivariate analysis. In 116 patients with primary intestinal NHL, 79 patients were men (68.1%) and 37 patients were women (31.9%). In the cases used in this study, 68 were B-cell NHL and 48 were T-cell NHL. The age, incidence of intestinal obstruction, B symptom and performance status (PS) were closely related with pathological subtype. One-year and two-year survival rates were 76.7 and 58.3%, respectively. The log-rank univariate analysis showed male patients, PS score greater than or equal to two, hypoproteinemia, intestinal perforation, T-cell type, late stage (III/IV), no radical surgery, and no chemotherapy had relatively poor prognoses. Cox multivariate analysis shown that gender (95.0% CI 0.218-0.721), pathological subtype (95.0% CI 1.484-4.179), and radical surgery (95.0% CI 0.110-0.394) were independent prognostic risk factor for primary intestinal NHL. Male patients, T-cell intestinal lymphoma, and no radical surgery had rapid clinical processes and poor prognoses.
Conventional transarterial chemoembolization (cTACE), drug-eluting beads (DEB-TACE) and transarterial radioembolization (TARE) are alternative strategies for unresectable hepatocellular carcinoma (HCC). However, which of these strategies is the best is still controversial. This meta-analysis was performed to evaluate the effects of DEB-TACE, TARE and cTACE in terms of overall survival (OS), tumor response and complications. A literature search was conducted using the EMBASE, PubMed, Google Scholar, and Cochrane databases from inception until July 2019 with no language restrictions. The primary outcome was overall survival, and the secondary outcomes included complete response and local recurrence. The comparison of DEB-TACE with cTACE indicated that DEB-TACE has a better OS at 1 year (RR 0.79, 95% CI 0.67-0.93, p = 0.006), 2 years (RR 0.89; 95% CI 0.81-0.99, p = 0.046), and 3 years (RR 0.89; 95% CI 0.81-0.99, p = 0.035). The comparison of TARE with cTACE indicated that TARE has a better OS than cTACE at 2 years (RR 0.87; 95% CI 0.80-0.95, p = 0.003) and 3 years (RR 0.90; 95% CI 0.85-0.96, p = 0.001). The comparison of DEB-TACE with TARE indicated that DEB-TACE has a better OS than TARE at 2 years (RR 0.40; 95% CI 0.19-0.84, p = 0.016). The current meta-analysis suggests that DEB-TACE is superior to both TARE and cTACE in terms of OS. TARE has significantly lower complications than both DEB-TACE and cTACE for patients with HCC. Further multicenter, well-designed randomized controlled trials are needed, especially for evaluating DEB-TACE versus TARE.
Colorectal carcinoma (CRC) is the one of the most common cancers with considerable metastatic potential, explaining the need for new drug candidates that inhibit tumor metastasis. The signal transducers and activators of the transcription 3 (Stat3) signaling pathway has an important role in CRC and has been validated as a promising anticancer target for CRC therapy. In the present study, we report our findings on nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3. Our studies showed that nifuroxazide decreased the viability of three CRC cell lines and induced apoptosis of cancer cells in a concentration-dependent manner. Moreover, western blot analysis demonstrated that the occurrence of its apoptosis was correlated with the activation of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, nifuroxazide markedly impaired CRC cell migration and invasion by downregulating phosphorylated-Stat3Tyr705, and also impaired the expression of matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, our studies showed that nifuroxazide also significantly inhibited the tumor metastasis in lung and abdomen metastasis models of colon cancer. Meanwhile, nifuroxazide functionally reduced the proliferation index, induced tumor apoptosis and impaired metastasis. Notably, nifuroxazide reduced the number of myeloid-derived suppressor cells in the blood, spleens and tumors, accompanied by the increased infiltration of CD8+ T cells in the tumors. Importantly, a marked decrease in the number of M2-type macrophages in tumor in the abdomen metastasis model was also observed. Taken together, our results indicated that nifuroxazide could effectively inhibit tumor metastasis by mediating Stat3 pathway and it might have a therapeutic potential for the treatment of CRC.
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