Advanced pancreatic cancer patients have poor prognosis and scarcely respond to conventional therapies. Clinical trials support the use of molecular-targeted therapy against epidermal growth factor receptor (EGFR) signaling. The objective of the current study was to evaluate the contribution of a monoclonal antibody against EGFR, nimotuzumab, to standard gemcitabine therapy. Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were assigned to receive gemcitabine plus nimotuzumab. The primary end point was overall survival, whereas the secondary end points included progression-free survival, objective response, and adverse side effects. A total of 18 eligible patients were accrued between December 2007 and July 2010. The disease control rate, calculated as the sum of complete response, partial response, and stable disease, was 55.6%. The median overall survival time was 9.29 months (95% CI, 5.499 to 13.072). The median progression-free survival was 3.71 months (95% CI, 2.526 to 4.902), and the 1-year survival rate was 38.9%. Of all the patients, 88.8% had at least one adverse side effect; however, no grade 4 adverse side effect was reported. Nimotuzumab as a high-purity humanized monoclonal antibody with favorable safety profile, its value in the treatment of pancreatic cancer along with gemcitabine, particularly in the comprehensive treatment of advanced pancreatic cancer, is appealing for further prospective randomized large-scale clinical trials.

Background: This study aimed to explore the prognostic value of angiogenesis-related genes (ARGs) and their association with immune cell infiltration (ICI) in breast cancer (BC).Methods: Transcriptome data of BC were obtained from the TCGA and GEO databases. Differentially expressed ARGs were identified by the limma package. The identification of key genes and construction of the risk score model were performed by univariate and multivariate Cox regression algorithms. The prognostic value of the risk score was assessed by ROC curves and nomogram. GO, KEGG pathway, and GSEA were used to investigate the biological functions of differentially expressed genes (DEGs), and CIBERSORT, ssGSEA, and xCell algorithms were performed to estimate the ICI in high-risk and low-risk groups. The correlations between prognostic biomarkers and differentially distributed immune cells were assessed. Moreover, a ceRNA regulatory network based on prognostic biomarkers was constructed and visualized by Cytoscape software.Results: A total of 18 differentially expressed ARGs were identified between tumor and adjacent normal tissue samples. TNFSF12, SCG2, COL4A3, and TNNI3 were identified as key prognostic genes by univariate and multivariate Cox regression analyses. The risk score model was further constructed based on the four-gene signature and validated in GSE7390 and GSE88770 datasets. ROC curves and nomogram indicated that the risk score had good accuracy for determining BC patient survival. Biological function analysis showed that DEGs in high- and low-risk groups had a high enrichment in immune-related biological processes and signaling pathways. Moreover, significantly different ICIs were found between high- and low-risk groups, such as memory B cells, CD8+ T cells, resting memory CD4+ T cells, follicular helper T cells, regulatory T cells, monocytes, M2 macrophages, and neutrophils, and each prognostic biomarker was significantly correlated with one or more immune cell types.Conclusion: The current study identified novel prognostic ARGs and developed a prognostic model for predicting survival in patients with BC. Furthermore, this study indicated that ICI may act as a bond between angiogenesis and BC. These findings enhance our understanding of angiogenesis in BC and provide novel guidance on developing therapeutic targets for BC patients.

NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; P<0.001). Therefore, monitoring serum Abs against NY-ESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC.

Background and purpose Stereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm). Materials and methods A systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity. Results After a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED10 of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively. Conclusion The study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.