Histone deacetylase inhibitor ITF2357 (givinostat) reverts transformed phenotype and counteracts stemness in in vitro and in vivo models of human glioblastoma In the original publication, the 6th author’s first name and the last name was inverted and incorrectly published. The correct author name is Letizia Ferella.

Answer to the letter to the editors by Matthes and colleagues regarding our systematic reviews on mistletoe

Letter to the editors of the Journal of Cancer Research and Clinical Oncology

Selective radiofrequency ablation of tumor by magnetically targeting of multifunctional iron oxide–gold nanohybrid Abstract Purpose Radiofrequency (RF) ablation therapy is of great interest in cancer therapy as it is non-ionizing radiation and can effectively penetrate into the tissue. However, the current RF ablation technique is invasive that requires RF probe insertion into the tissue and generates a non-specific heating. Recently, RF-responsive nanomaterials such as gold nanoparticles (AuNPs) and iron oxide nanoparticles (IONPs) have led to tremendous progress in this area. They have been found to be able to absorb the RF field and induce a localized heating within the target, thereby affording a non-invasive and tumor-specific RF ablation strategy. In the present study, for the first time, we used a hybrid core-shell nanostructure comprising IONPs as the core and AuNPs as the shell (IO@Au) for targeted RF ablation therapy. Due to the magnetic core, the nanohybrid can be directed toward the tumor through a magnet. Moreover, IONPs enable the nanohybrid to be used as a magnetic resonance imaging (MRI) contrast agent. Results In vitro cytotoxicity experiment showed that the combination of IO@Au and 13.56-MHz RF field significantly reduced the viability of cancer cells. Next, during an in vivo experiment, we demonstrated that magnetically targeting of IO@Au to the tumor and subsequent RF exposure dramatically suppressed the tumor growth. Conclusion Therefore, the integration of targeting, imaging, and therapeutic performances into IO@Au nanohybrid could afford the promise to improve the effectiveness of RF ablation therapy.

Protective effect of the “food-microorganism-SCFAs” axis on colorectal cancer: from basic research to practical application Abstracts Background Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC). Aims This study aims to elucidate the “food-microorganism-SCFAs” axis and to provide guidance for prevention and intervention in CRC. Methods The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening. Results The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The “food-microorganism-SCFAs” axis was constructed by summarizing the pertinent literature. Conclusions This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.

Effects of surgery on survival of elderly patients with stage I small-cell lung cancer: analysis of the SEER database Abstract Introduction Surgery improves survival of small-cell lung cancer (SCLC) patients in early stage. However, the role of surgery in the elderly stage I SCLC patients is not well established. We designed this retrospective study to explore the efficacy of surgery on survival of this subset population. Patients and methods Elderly patients aged ≥ 75 years with stage I SCLC diagnosed histologically from 1998 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Included patients were divided into surgery group (received surgery, accompanied by chemotherapy, radiotherapy, or both or neither), non-surgical group (only received radiotherapy, chemotherapy, or combination), and untreated group. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among the three groups by the Kaplan–Meier analysis. Cox proportional hazards regression was used to identify factors associated with survival. Results A total of 983 patients were included. Among all of the patients, 24.0% patients received surgery, 46.6% patients received non-surgical treatment, and 29.4% patients received no treatment. The 5-year OS rates of surgery, non-surgical and untreated groups were 31%, 12% and 6%, respectively (P < 0.0001). In multivariable analysis, surgery was an important factor that improved OS when compared with non-surgical treatment (HR 0.554; 95% CI 0.458–0.670 [P < 0.0001]). In subgroup analysis, surgery remained an independent factor for OS among patients aged 75–79 years (HR 0.506; 95% CI 0.391–0.655 [P < 0.0001]) and 80–84 years (HR 0.544; 95% CI 0.388–0.763 [P < 0.0001]), while did not reach statistical significance when compared to non-surgical treatment for patients age ≥ 85 years (HR 0.914; 95% CI 0.507–1.650; [P = 0.766]). Conclusion Surgical resection significantly improved OS in stage I SCLC patients aged 75–84 years in our study, but further exploration in larger prospective clinical trials is needed.

A comparison of regorafenib and fruquintinib for metastatic colorectal cancer: a systematic review and network meta-analysis Abstract Background The optimal treatment in the third-line and later-line setting for metastatic colorectal cancer (mCRC) has not been established. As reported, regorafenib and fruquintinib have shown to be superior to placebo in mCRC. However, no direct clinical comparison of regorafenib and fruquintinib has been conducted; we performed a systematic review and network meta-analysis to compare the efficacy and safety of regorafenib and fruquintinib. Methods PubMed, Embase, and the Cochrane Library were systematically searched and randomized-controlled trials (RCTs) assessing the effect and safety of regorafenib or fruquintinib versus placebo for patients with mCRC were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. After that, we performed pairwise direct meta-analyses (regorafenib vs. placebo and fruquintinib vs. placebo) and indirect comparison (regorafenib vs. fruquintinib) using network meta-analyses methods. Results Three RCTs involving 1380 patients were included in the meta-analysis. In the direct meta-analysis, regorafenib and fruquintinib both showed survival benefits when compared with placebo. For the indirect comparison, fruquintinib shows no significant difference in OS compared to regorafenib (HR 0.97; 95% CI 0.64–1.46). Regarding PFS, there was a tendency that fruquintinib was superior to regorafenib (HR 0.65; 95% CI 0.39–1.08); however, there was no statistic difference. For the safety analysis, in indirect comparison, fruquintinib showed significant difference in all-grade toxicity compared to regorafenib (OR 0.73; 95% CI 0.65–0.82), especially in subgroup of proteinuria (OR 0.31; 95% CI 0.11–0.86). For the grade 3–5 toxicity, fruquintinib showed no significant difference when compared with regorafenib (OR 0.92; 95% CI 0.64–1.32). Conclusion Based on efficacy and safety, there was a tendency that fruquintinib was superior to regorafenib, as a whole, regorafenib and fruquintinib demonstrated similar clinical benefit for patients with refractory mCRC. It seems that fruquintinib has less toxic in all-grade toxicity when compared with regorafenib.

REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression Abstract Objectives Recent research has classified lung adenocarcinoma patients with KRAS mutation into three subtypes by co-occurring genetic events in TP53 (KP subgroup), STK11/LKB1 (KL subgroup) and CDKN2A/B inactivation plus TTF-1 low expression (KC subgroup). The aim of this study was to identify valuable biomarkers by searching the candidate molecules that contribute to lung adenocarcinoma pathogenesis, especially KC subtype. Materials and methods We analyzed the publicly available database and identified the candidate REG4 using the E-GEOD-31210 dataset, and then confirmed by TCGA dataset. In addition, an independent cohort of 55 clinical samples was analyzed by quantitative real-time PCR analysis. Functional studies and RNA sequencing were performed after silencing the REG4 expression. Results REG4, an important regulator of gastro-intestinal carcinogenesis, was highly expressed in KRAS mutant lung adenocarcinoma with low expression of TTF-1 (KC subtype). The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. Further in vitro and in vivo functional assays revealed silencing REG4 expression significantly reduces cancer cell proliferation and tumorigenesis. Moreover, RNA sequencing and GSEA analysis displayed that REG4 knockdown might induce cell cycle arrest by regulating G2/M checkpoint and E2F targets. Conclusion Our results indicate that REG4 plays an important role in KRAS-driven lung cancer pathogenesis and is a novel biomarker of lung adenocarcinoma subtype. Future studies are required to clarify the underlying mechanisms of REG4 in the division and proliferation of KC tumors and its potential therapeutic value.

Weight loss and body mass index in advanced gastric cancer patients treated with second-line ramucirumab: a real-life multicentre study Abstract Aims and methods This multicenter retrospective study aims to evaluate the correlations between Body Weight Loss (BWL), Body Mass Index (BMI) and clinical outcomes (ORR, PFS, and OS) of advanced gastric cancer (aGC) patients treated with second-line ramucirumab-based therapy in a “real-life” setting. Results From December 2014 to October 2018, 101 consecutive aGC patients progressed to a first-line chemotherapy were treated with ramucirumab alone (10.9%) or in combination with paclitaxel (89.1%). Median BMI was 21.2 kg/m2 and mBWL since first-line treatment commencement was 4.5%. Among 53 patients who underwent primary tumor resection (PTR), 73.6% experienced BWL, while 26.4% did not experience BWL (p = 0.0429). Patients who underwent PTR had a significantly higher probability of experiencing BWL (yes vs no) [OR = 2.35 (95% CI 1.02–5.42), p = 0.0439]. Among the 89 evaluable patients, ORR was 26.9% (95% CI 17.2–40.1). At a median follow-up of 17.3 months, mPFS was 5.4 months (95% CI 3.6–6.8) and mOS was 8.7 months (95% CI 7.3–11.9). In the multivariate analysis, only ECOG-PS and BMI were confirmed independent predictors for shorter PFS [HR = 1.69 (95% CI 1.01–2.82), p = 0.04] [HR = 1.97 (95% CI 1.12–3.46), p = 0.01] and OS [HR = 1.69 (95% CI 1.01–2.83), p = 0.04] [HR = 2.08 (95% CI 1.17–3.70), p = 0.01]. Conclusion Efficacy of ramucirumab is confirmed in this “real-life” analysis. BWL seems not to have correlations with clinical outcomes in these patients, while BMI and ECOG-PS remain major prognostic factors. A possible explanation for the lack of prognostic effect of BWL might be the proportion of patients subjected to PTR in this series (52.5%).

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients Abstract Purpose Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. Methods Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1–3 intravenously. Results After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3–4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS. Conclusions The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.