OBJECTIVE:To evaluate the conversion to resection rate (CTRR), treatment safety and short-term oncological outcomes of FOLFOX-hepatic arterial infusion chemotherapy (FOLFOX-HAIC) plus intravenous bevacizumab or cetuximab for initially unresectable colorectal liver metastasis (IU-CRLM). METHODS:Data from a consecutive cohort of IU-CRLM patients who underwent conversion treatment using FOLFOX-HAIC with bevacizumab or cetuximab in Tongji Hospital were reviewed. The CTRR, tumor response, safety of drug treatment and surgery, potential predictive factors, and short-term oncological outcomes were got to preliminarily evaluate this conversion regimen. RESULTS:A consecutive cohort of 42 patients were screened, and finally, 19 patients were enrolled in the study. 13 patients successfully underwent liver resection, the CTRR was 68.4%. Patients in no resection group showed more ratio of prior chemotherapy and prior resection of primary tumor, reduced chemotherapy dose, worse tumor differentiation and more lymphvascular invasion than in resection group. Patients in resection group showed better tumor response, including overall response, objective response, largest tumor diameter and levels of tumor biomarkers after treatment, except for disease control rate, than in no resection group. The incidence of grade≥3 adverse event was 21.1% and no pharmacotherapy-related death occurred in HAIC. The median operative time was 265 min and no grade≥2 intraoperative incidents occurred. The incidence of postoperative complications was 23.1%, but serious complication rate was only 7.7% and no death occurred with 90 days after surgery. CONCLUSION:FOLFOX-HAIC was an effective and safe conversion treatment for IUCRLM without extrahepatic metastasis.

4176 Background: Extrapulmonary neuroendocrine carcinoma (EP-NEC) is a poorly differentiated and highly aggressive malignancy with poor prognosis. Platinum (cisplatin or carboplatin) plus etoposide (EC/EP) remains the standard first-line regimen. However, clinical outcomes are suboptimal, highlighting the need for more effective strategies. Camrelizumab is a programmed cell death-1 (PD-1) inhibitor, and apatinib is a vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor. Both have demonstrated antitumor activity in multiple solid tumors. Therefore, we investigated a sequential regimen consisting of induction EC/EP plus camrelizumab followed by maintenance camrelizumab plus apatinib in treatment-naive patients with advanced or metastatic EP-NEC. Methods: This multicenter, single-arm trial enrolled patients with previously untreated advanced or metastatic EP-NEC. Patients received 4–6 cycles of induction therapy with cisplatin (25 mg/m² iv, d1-3, q3w) or carboplatin (AUC = 5 iv, d1, q3w) plus etoposide (100 mg/m² iv, d1-3, q3w) in combination with camrelizumab (200 mg iv, d1, q3w). Patients without disease progression received maintenance camrelizumab (200 mg iv, q3w) plus apatinib (250 mg, qd) until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Tumor response was assessed every 6 weeks per RECIST v1.1. The trial is registered on ClinicalTrials.gov, NCT05142865. Results: As of January 2026, 30 patients were enrolled (median age of 59.5 years, range 30–73), and all 30 patients were evaluable for efficacy. The ORR was 66.7% and the DCR was 83.3%. Median PFS was 9.87 months (95% CI, 6.23–NA). Median OS was not reached, and the 1-year OS rate was 74.6%. All patients experienced adverse events (AEs), with grade ≥3 AEs observed in 43.3% (13/30). Grade ≥3 AEs were mainly hematologic toxicities, including anemia (13.3%), neutropenia (13.3%) and thrombocytopenia (13.3%). Common non-hematologic AEs included elevated transaminases (43.3%), mainly grade 1–2, with grade ≥3 events in 10.0%. Conclusions: Induction EC/EP plus camrelizumab followed by maintenance camrelizumab plus apatinib showed encouraging activity and manageable safety in treatment-naive advanced or metastatic EP-NEC. Further studies are warranted to confirm these findings. Clinical trial information: NCT05142865 .

Gut microbiome plays a pivotal role in modulating immunotherapy responses in colorectal cancer (CRC) treatment. While individual enterobacteria have been identified as enhancers of anti-PD-1/anti-PD-L1 therapy, the synergistic effects of multiple probiotic strains remain insufficiently explored. In this study, we investigated the therapeutic potential of Tumor-Suppressing Multi-Enterobacteria (TSME), a consortium of nine beneficial intestinal probiotic strains, in enhancing anti-PD-1/anti-PD-L1 therapy for microsatellite stable (MSS) CRC. Using a tumor-bearing mouse and employing techniques including flow cytometry, immunohistochemistry, ELISA, and genomic sequencing, we found that TSME significantly improved the efficacy of immune checkpoint inhibitors (ICIs) by optimizing tumor immune and microbe microenvironment. Specifically, the addition of TSME increased CD8+ T cell infiltration and reshaped cytokine profiles, including reducing pro-inflammatory cytokines (IL-17, IL-1β, IL-6, and TNF-α) while elevating anti-inflammatory factors (IFN-γ). Moreover, TSME significantly up-regulated key immune pathways, including TNF signaling, cytokine-cytokine receptor interaction, and JAK-STAT signaling. In addition, TSME restructured the gut microbiome, increasing the abundance of beneficial bacteria such as Akkermansia and Alistipes. These findings highlight the synergistic effect of the multi-strain probiotics in enhancing ICI efficacy. Well-formulated probiotic consortia offer a promising strategy for enhancing immunotherapy outcomes in MSS CRC and advancing broader implementation of microbiome-assisted precision oncology.

The efficacy and safety of conventional first-line chemotherapeutic regimens for the treatment of advanced biliary tract carcinomas (ABTCs) have been unsatisfactory. We aimed to explore alternative chemotherapeutic regimens capable of providing improved efficacy and fewer side-effects. Multicentre, randomised, phase II clinical trial. Patients with unresectable advanced-stage tumors, or those who have developed recurrence or metastasis following initial radical surgery, between January 2021 and November 2022 were included. The participants were randomised to either a gemcitabine-cisplatin group (GC) or an albumin-paclitaxel-cisplatin group (NC). Progression-free survival (PFS) was the primary outcome, whereas overall survival (OS), and objective response rate (ORR) were the secondary outcomes. The trial enrolled 75 patients and had a median follow-up period of 11 months. The median PFS (mPFS) was 7.8 m (95 https://www.chictr.org.cn/showproj.html?proj=38440 .

Programmed death 1 (PD-1) and its ligand PD-L1 inhibitors and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies have been approved for the treatment of advanced hepatocellular carcinoma (HCC), but the response rates of these immunotherapy are not high, and they are easy to be resistant. Studies have shown that the gut microbiota can significantly influence immune responses and the efficacy of immune checkpoint inhibitors (ICIs). The aim of this study is to investigate whether the combination therapy of Tumor-Suppressing Multi-Enterobacteria (TSME) and PD-L1 inhibitor (atezolizumab) can improve the efficacy of immunotherapy-resistant hepatocellular carcinoma. Patients with advanced liver cancer resistant to atezolizumab were treated with tumor suppressor TSME combined with atezolizumab, and the efficacy was evaluated. By establishing a tumor-bearing mouse model, the control group, InVivoMAb anti-mouse PD-1 monotherapy group, TSME group, and anti-PD-1 mab +TSME double drug group were set up. To evaluate whether the combination therapy enhances the antitumor effect, the proportion of T cells in the tumor microenvironment (TME) was analyzed by immunohistochemistry. Patients with clinically immuno-resistant hepatocellular carcinoma who were treated with TSME still had a PFS of about 7 months with continued atezolizumab treatment, and they were still in long-term survival. The in vivo model showed that TSME combined with αPD-1 promoted the efficacy of anti-PD-1 antibody immunotherapy by increasing the proportion of CD8+ T cells and CD4+ T cells in the tumor microenvironment and reducing the proportion of regulatory T cells (Tregs) compared with TSME alone or αPD-1 alone. The relative tumor inhibition rate (TGI) of αPD-1+TSME combination group was as high as 58.78% ± 7.55%. Tumor volume was lower in the αPD-1+TSME group than in the monotherapy group. Anti-tumor TSME combined with αPD-1 mAb may be a new strategy to improve the sensitivity of immune-resistant patients with advanced hepatocellular carcinoma to anti-PD-1 immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) or programmed death ligand 1(PD-L1) respond well to deficient-microsatellite(dMMR) colorectal cancer and poorly to proficient-microsatellite (pMMR) CRC. Anti-vascular therapy is the standard backline treatment regimen for advanced metastatic colorectal cancer and also potentiates the immunotherapeutic efficacy of CRC by promoting immune cell infiltration and remodeling the tumor immune microenvironment (TIME). However, it is not clear whether combining radiotherapy, anti-vascular and anti-PD-1 can affect the efficacy of pMMR CRC. In this experiment, we investigated the antitumor efficacy of radiotherapy combined with fruquintinib and tirelizumab in pMMR CRC mice. CT26 cellular hormonal tumor corresponding to pMMR CRC. A mouse model with subcutaneous transplanted tumors is established, divided into control, radiotherapy (IR), fruquintinib + tirelizumab (F+T), and radiotherapy + fruquintinib + tirelizumab (IR+F+T) groups. Immunofluorescence (IF) experiments were conducted to investigate the number and function of tumor vessels. Immunohistochemistry (IHC) and flow cytometry (FC) were utilized to examine immune cell infiltration and alterations within the TIME. Compared to the control group, tumor growth was significantly inhibited after treatment. When compared to IR and F+T, IR+F+T demonstrated a remarkable suppression of tumor growth. The quantitative analysis results showed a significant decrease in Ki-67 positive cells in the target tumors with IR+F+T compared to IR and F+T. The TUNEL results indicated that treatment promoted tumor cell apoptosis, and the effect was further enhanced with triple combinational therapy. Both F+T and IR+F+T repressed CD31 expression and improved the ratio of α-SMA+/CD31+ in tumor tissue, yet there was no significant difference between the two groups. The immunohistochemistry and flow cytometry results demonstrated that triple combinational therapy increased tumor-infiltrating CD8+ T cells and significantly elevated the proportions of CD8, CD69, and CD86. Both F+T and IR+F+T boosted PD-L1 expression, with no significant difference between them. Combined irradiation on top of fruquintinib and tirelizumab treatment enhanced the efficiency in CT26 murine CRC syngeneic tumor model. There was no significant effect of radiotherapy on the anti-angiogenesis of fruquintinib and the promotion of normal vascular function. Irradiation promoted CD8+ T cell and dendritic cell infiltration and activation. Mingsheng Zhang, Qingqing Yu, Huiying Hou, Xiaoting Su, Qin Huang, Hong Qiu, Le Huang, Liang Zhuang, Qiang Fu, Yanmei Zou, Li Sun, Liu Huang, Shunfang Liu, Fei Liu, Xianglin Yuan. Efficacy and mechanism of radiotherapy combined with fruquintinib and tirelizumab in mCRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1828.

150 Background: MSS patients (pts) account for the majority of all CRC pts and show poor response to immunotherapy. While fruquintinib plus PD-1 inhibitors is an effective option for MSS CRC pts in China who are refractory to multiple lines of therapy. In addition, immunomodulatory effects of stereotatic body radiotherapy (SBRT) have demonstrated in previous studies. Here, we report FRUIT trial of fruquintinib combined with tislelizumab and SBRT as a later-line therapy in MSS mCRC pts. Methods: In this single-arm, open-label, single-center, phase II trial (NCT04924179), we included mCRC pts who have failed with at least second-line therapy. Eligible pts undergo the following regimens on a 21-days cycle: fruquinitib (5mg, QD, PO, d1-14) plus tislelizumab (200mg, d1, I.V.) and SBRT (8-10Gy×5F, QOD). The primary endpoint is progression-free survival (PFS), and secondary endpoints are disease-control rate (DCR), objective response rate (ORR), overall survival (OS), and safety. The responses are evaluated according to RECIST Version 1.1 and adverse events are evaluated by CTCAE v5.0. Results: AS of August 31, 2022, 24 pts were included in the trial and 23 (11 male; media age 60 years; all pts with MSS; 7 had received 3 prior lines of therapy) in the efficacy analysis. 87%, 9% and 17% pts had received bevacizumab, regorafenib and cetuximab in previous therapy, respectively. Among 23 pts, median follow-up was 7.8 mo (95%CI: 4.31, 11.29). The median PFS was 5.1mo (95%CI: 0.57-9.63), with 9 pts still on treatment at data cutoff. 6pts achieved partial response (PR), 13 stable disease (SD), illustrating an ORR of 26% and a DCR of 83%. Adverse events (AEs) occurred in 22 (96%) pts which were mostly grade 1/2. 17% pts experienced a grade 3/4 AEs, including hypertension (9%), hand foot skin reaction (4%) and thrombocytopenia (4%). The combination regimen was well tolerate. Conclusions: Fruquintinib plus tislelizumab and SBRT as a later-line therapy in refractory MSS mCRC pts shows a promising clinical benefit, with a manageable safety profile, which suggests a potential new paradigm for therapy in MSS mCRC pts. Clinical trial information: NCT04924179 .

Background: This study aimed to investigate the superiority of nab -paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC). Methods: In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS ( nab -paclitaxel 260 mg/m 2 on day 1 or 130 mg/m 2 on days 1 and 8; oral S-1 40–60 mg twice daily for 14 days) or SOX (130 mg/m 2 oxaliplatin on day 1; oral S-1 40–60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety. Results: Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39–32.87]. The median PFS was 9.03 months (95% CI, 6.50–11.56) in the AS group and 5.07 months (95% CI, 4.33–5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37–0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group. Conclusion: Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities. Trial registration: Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.

Background:At present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies.Methods:The records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5-2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded.Results:The baseline clinical characteristics of the patients were broadly similar among the three groups. The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5-5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9-4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1-2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4-11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3-10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2-10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant.Conclusions:Low-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.

282 Background: Albumin-bound paclitaxel has been proven to be an active agent in advanced gastric cancer, and was approved by PMDA Japan for use as a second-line treatment of advanced gastric cancer. The aim of this study was to evaluated the efficacy and safety of AS and SOX in the first-line treatment of advanced gastric cancer. Methods: Patients diagnosed with unresectable locally advanced, recurrent or metastatic human epidermal growth factor receptor type 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma were randomized (1:1) to either AS group (albumin-bound paclitaxel 260mg/m2 d1 or 130mg/m2 d1, 8; S-1 40 mg [BSA < 1.25 m2], 50 mg [1.25 ≤ BSA < 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks) or SOX group (oxaliplatin 130mg/m2 d1; S-1 40 mg [BSA < 1.25 m2], 50 mg [1.25 ≤ BSA < 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks). Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: Between March 2019 and March 2021, 96 patients were enrolled and 85 patients (AS group, n = 43; SOX group, n = 42) who received at least one dose of study drug and had at least one postbaseline efficacy evaluation were included in the final analysis. 34 (79.0%) patients in the AS group and 35 (83.3%) in the SOX group had discontinued treatment. Of these 85 patients, 78.8% had two or more organs involved, 61.2% had peritoneal dissemination, and more than 1/4 had massive ascites. Patient demographics and disease characteristics were generally balanced between arms. With median follow-up 15.4 months (95% CI, 8.8-21.9), the median PFS of AS group vs. SOX group was 9.2 vs.5.1 months (HR = 0.58 [95% CI 0.36-0.96], p = 0.034); and the median OS was 14.4 vs. 15.4 months (HR = 0.73 [95%CI 0.40-1.34], p = 0.375). Tumor response was assessable in 33 patients according to RECIST V1.1 in both cohorts, the ORR and DCR were similar in AS vs. SOX arm (ORR: 54.5% vs. 51.5%, P = 0.805; DCR: 78.8% vs. 78.8%, P = 1.000). The main grade 3 or worse treatment-related adverse events were neutropenia (30.2% vs 23.8%), Leucopenia (11.6% vs 11.9%) and peripheral sensory neuropathy (4.7% vs 7.1%) in AS and SOX group. The study was planned to be adjusted, due to the widespread use of immunotherapy in first-line treatment of gastric cancer. Conclusions: The results of this study indicated that in previously untreated patients with unresectable locally advanced, recurrent or metastatic HER2-negative gastric or GEJ adenocarcinoma, AS achieved better PFS than SOX, with an inadequate power. The toxicities were controllable and consistent with previously reported. Clinical trial information: NCT03801668.

目的 探讨虚拟现实技术联合案例教学法在肿瘤康复治疗师教学中的应用效果.方法 选取2018年1—12月在华中科技大学同济医学院附属同济医院肿瘤科和康复医学科接受肿瘤康复培训的48名康复治疗师为对象,根据随机数字表法分为试验组(24例)和对照组(24例),试验组采用虚拟现实技术联合案例教学法进行教学,对照组采用传统讲授式教学.课程结束后,对两组学员进行理论考核和操作考核、问卷调查教学满意度,综合评价虚拟现实技术联合案例教学法在肿瘤临床康复治疗师教学中的应用效果.结果 试验组康复治疗师的理论考核成绩和操作考核成绩明显高于对照组[试验组理论基础知识(82.48±6.98)分,操作考核如运动治疗(16.62±2.89)分等](P<0.05).同时,试验组在教学满意度多维度调查评估表各项评分均明显高于对照组[试验组兴趣吸引力(4.28±0.62)分、理解记忆力(4.14±0.66)分、沟通能力培养(4.09±0.60)分等](P<0.05).结论 虚拟现实技术联合案例教学法在肿瘤康复治疗师教学中的应用能提升教学质量和教学满意度,培养全面的理论基础知识、操作实践能力和沟通能力.

Colorectal cancer (CRC) is the fifth most common cancer and one of the leading causes of cancer-related death in China. Although apatinib and S-1, respectively, are used in the treatment of advanced colorectal cancer, the efficacy and safety of the combination of the two drugs are unclear. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies. Records of 114 patients with refractory mCRC in our center from April 2016 to 17 September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250mg/day combined with S-1, 36 received regorafenib starting at 80mg/day with weekly escalation, and 35 received fruquintinib. The median progression-free survival was 3.9 months [95% confidence interval (CI),2.5-5.3 months] in the apatinib plus S-1 group, 3.1 months (95% CI 1.9-4.2 months) in the fruquintinib group, and 2.4 months (95% CI 2.1-2.7 months) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib. The median overall survival was 8.2 months (95%CI，5.4-11.0 months) in the apatinib plus S-1 group, 7.8 months (95%CI，5.3-10.3 months) in the fruquintinib group, and 7.5 months (95%CI, 4.2-10.7 months) in the regorafenib group, which was comparable among the three groups. Disease control rate (DCR) was 83.7% in the apatinib plus S-1 group, 71.4% in the fruquintinib group, and 66.7% in the regorafenib group, and no significant difference was shown among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia, leukopenia, and thrombocytopenia, and the hand-foot skin reaction was more prevalent in the regorafenib group, while the adverse reaction of hypertension in the fruquintinib group was very significant. Low-dose apatinib plus S-1 prolonged PFS compared with regorafenib, and is a promising clinical regimen for the treatment of refractory mCRC with tolerable and controlled toxicity that is worth studying in the future.

Angiogenesis has been certified to account for tumor pathobiology. Circular RNAs (circRNAs) have been demonstrated to be involved in angiogenesis-related diseases, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory roles of most circRNAs remain obscure. This study aims to uncover the function of hsa_circ_0004018 on angiogenesis in HCC. Firstly, quantitative real-time RT-PCR (RT-qPCR) analyzed that circ_0004018 was definitely down-regulated in HCC. Western blot analysis was conducted to detect the protein level of fused protein in sarcoma (FUS) and TIMP metallopeptidase inhibitor 2 (TIMP2). Functional assays were carried out to assess the impacts of circ_0004018 on HCC. From the experimental results, we found that overexpression of circ_0004018 significantly inhibited angiogenesis in HCC. The regulatory mechanism of circ_0004018 in HCC was determined by chromatin immunoprecipitation (ChIP), luciferase reporter assays and RNA immunoprecipitation (RIP) assay. Therefore, we proved that estrogen receptor 1 (ESR1) mediated circ_0004018 regulated TIMP2 by recruiting FUS. A series of rescue assays verified that circ_0004018 participated in angiogenesis in HCC via modulating TIMP2. In summary, this paper disclosed that ESR1 activated circ_0004018 inhibited angiogenesis in HCC via binding to FUS and stabilizing TIMP2 expression.

Hereditary medullary thyroid carcinoma (MTC) is mainly caused by germline mutations in the RET proto-oncogene, which accounts for 20–30% of all MTC according to foreign studies. However, no English literatures have reported Chinese hereditary MTC. Here, we reported two Chinese brothers with MTC that caused by germline RET mutation. The younger brother was diagnosed with MTC at 29 years ago and suffered recurrence more than 10 years. For elder brother, the diagnosis of MTC was made by postoperative pathological examination at age 61. Both patients received total thyroidectomy and lymph node dissection. Since they had a significant family history for MTC, genetic detection was performed and identified a germline mutation in RET exon 10 (p.C620Y). This mutation was also detected in their offspring, indicating a moderate risk of MTC. This is the first report presenting a Chinese family with hereditary MTC caused by the RET p.C620Y variant. This case series emphasize the importance of genetic detection of RET proto-oncogene for MTC patients, and bring out managements for individuals after detection of RET mutations.

目的 探讨培菲康联合复方小檗碱保留灌肠预防急性放射性直肠炎的临床疗效.方法 选择2016年1月—2017年12月我院收治的直肠癌根治术后行辅助放化疗的100例患者为研究对象,随机分为观察组(n=50)和对照组(n=50).两组患者均接受卡培他滨(825 mg·m-2,2次/天,口服)同期放疗(DT 45 Gy/25 F),观察组在此基础上采用培菲康口服(2包/次,3次/天)联合复方小檗碱保留灌肠(20 mL/次/天).比较两组患者急性放射性直肠炎的发生情况、卡氏功能状态(KPS)评分、乏力状况及生活质量(QOL)评分.结果 治疗4周时,观察组患者急性放射性直肠炎的发生率和级别均明显低于对照组(P<0.05);观察组患者KPS评分(80.02±7.34)显著高于对照组(76.64±7.08)(P<0.05);观察组患者中重度乏力的发生率(20％)显著低于对照组(48％)(P<0.05);观察组患者QOL评分(41.26±5.08)显著高于对照组(39.02±4.90)(P<0.05).观察组因放射性肠炎而减少口服化疗药物剂量或中断放疗的比例(4％)均显著低于对照组(18％)(P<0.05).结论 培菲康联合复方小檗碱保留灌肠对预防急性放射性直肠炎效果较好,患者依从性好,值得临床推广应用.

Osteosarcoma is the most common primary malignant tumor of the bone in adolescents and children, with high rates of metastasis and a poor prognosis. Recently, osteosarcoma cancer stem/stem-like cells (CSCs) have been identified as the main cause of recurrence and metastasis. Stress-induced phosphoprotein 1 (STIP1), a co-chaperone that binds to heat shock proteins 70 and 90, is abnormally expressed in several tumor cell lines, and may play an important role in tumor cell migration and invasion. These features indicate that STIP1 may represent a new therapeutic target for osteosarcoma CSCs. However, the role of STIP1 in osteosarcoma CSC migration and invasion remains largely unknown. In the present study, CD133-positive osteosarcoma CSCs were first isolated and cultured by magnetic cell sorting and serum-free medium suspension cell sphere culture, respectively. Knockdown of STIP1 by small interfering RNA significantly was then shown to inhibit the migration and invasion of these cells, possibly due to the regulation of the expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase-2. Furthermore, data from the present study suggested that the knockdown of STIP1 decreased the levels of phosphorylated Akt and phosphorylated ERK1/2. In summary, these findings indicate that targeting STIP1 in osteosarcoma may constitute a viable molecular targeted therapy strategy for the inhibition of CSC invasion and migration.

IMPORTANCE Fluorouracil-based chemotherapy combined with anti-epidermal growth factor receptor/vascular endothelial growth factor therapy is the standard first-line treatment for metastatic colorectal cancer followed by low-intensity maintenance therapy to balance the clinical efficacy and adverse effects (AEs). However, there have been concerns about the AEs of capecitabine plus cetuximab as a maintenance therapy in patients with RAS wild-type metastatic colorectal cancer. OBJECTIVE To evaluate the biological activity and safety of capecitabine plus cetuximab as a novel maintenance therapy for RAS wild-type metastatic colorectal cancer. Design, Setting, and PARTICIPANTS This phase 2 prospective clinical trial was conducted from April 29, 2016, to April 29, 2019, at 5 centers in China. Patients diagnosed as having RAS wild-type metastatic colorectal cancer were recruited to receive fluorouracil-based cytotoxic agents combined with cetuximab followed by capecitabine plus cetuximab for maintenance therapy. Forty-seven patients with histologically confirmed metastatic colorectal cancer and genetic test results showing a wild-type RAS were enrolled in maintenance therapy. INTERVENTIONS Induction therapy for patients with RAS wild-type metastatic colorectal cancer was 8 to 12 cycles of fluorouracil-based chemotherapy combined with cetuximab. After stable disease status or better was achieved, reduced-dose capecitabine plus cetuximab was administered for maintenance therapy. MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival during maintenance therapy. The secondary end points were total progression-free survival, overall survival, quality of life, safety, and toxic effects of treatment. RESULTS Forty-seven patients were enrolled in maintenance therapy, with a median age of 52 years (range, 25-81 years) and 32 (68%) of them being men. The median maintenance progression-free survival was 7.2 (95% CI, 5.8-8.6) months. The median progression-free survival was 12.7 (95% CI, 11.8-15.4) months. The median overall survival was 27.4 (95% CI, 21.4-35.5) months. Grade 3 to 4 AEs during induction therapy included neutropenia (4 patients [9%]), diarrhea (4 patients [9%]), nausea or vomiting (3 patients [6%]), rash acneiform (10 patients [21%]), and hand-foot syndrome (8 patients [17%]). Grade 3 to 4 AEs during maintenance therapy included diarrhea (2 patients [4%]), rash acneiform (8 patients [17%]), and hand-foot syndrome (5 patients [11%]). CONCLUSIONS AND RELEVANCE Reduced-dose capecitabine plus cetuximab after initial chemotherapy is a novel maintenance therapy for patients with RAS wild-type metastatic colorectal cancer that achieved good outcomes and tolerable nonserious AEs.

Irinotecan-based chemotherapy is a fundamental cytotoxic regimen for advanced colorectal cancer. The disposition of irinotecan is known to vary in a fashion partially depending on genetic variations in the drug metabolic pathways. UDP-glucuronosyltransferase (UGT)1A1 is a predominant enzyme that converts the active metabolite of irinotecan to the inactive form via a glucuronidation process. Several UGT1A1 polymorphisms are linked to SN-38 glucuronidation and irinotecan-related adverse events, while the predictive role of UGT1A1 polymorphisms regarding therapeutic outcome is controversial. In this review, we will evaluate the impact of UGT1A1 genotypes on irinotecan-induced toxicity and therapeutic efficacy in colorectal cancer patients receiving irinotecan-based treatment.

目的 探讨营养预后指数与接受替吉奥联合阿帕替尼治疗的晚期三线结直肠癌患者的疗效的相关性.方法 回顾性收集接受阿帕替尼联合替吉奥治疗的43例三线结直肠癌患者的临床资料,计算预后营养指数(PNI)、白蛋白/球蛋白比值(AGR)、中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)以及淋巴细胞/单核细胞比值(LMR)等营养免疫评估指标,采用Cox比例风险回归模型及Kaplan-Meier生存曲线评价相关免疫营养指标对于患者生存的影响.结果 根据总生存时间(IS)的受试者工作特征曲线(ROC)曲线分析,PNI最佳临界值定义为47.08;单因素分析结果显示,美国东部肿瘤协作组(ECOG)评分、PNI、AGR、血红蛋白(HGB)、NLR及LMR与患者OS显著相关;多变量分析显示ECOG评分及PNI是OS的独立预后因素.低PNI患者中位生存时间(mOS)为5.70个月(95％ CI =4.42 ～6.98),高PNI患者mOS为15.77个月(95％ CI=7.43 ～24.1),P=0.000;低PNI的患者中位无进展生存时间(mPFS)为3.42个月(95％ CI=2.31 ～4.53),高PNI患者mPFS为6.29个月(95％ CI=4.96 ～7.62),P=0.003.结论 PNI在作为晚期结直肠癌接受替吉奥联合阿帕替尼三线治疗的生存预测方面具有较好临床应用价值,简单易行.

Angiogenesis has always been the topic of major scientific interest in the field of malignant tumors. Nowadays, targeting angiogenesis has achieved success in various carcinomas by several mechanisms, including the use of anti-angiogenic small molecule receptor tyrosine kinase inhibitors (TKIs). The development of TKIs targeting pro-angiogenic receptors, mainly vascular endothelial growth factor receptor (VEGFR) family, have significantly improved the outcome of certain types of cancers, like renal cell carcinoma, hepatocellular carcinoma, and colorectal carcinoma. However, the general response rate is not very satisfactory. The particular toxicity profile and resistance to anti-angiogenic targeted agents are unavoidable, and no specific marker is available to screen responsive patients to TKIs for precision therapy. To date, about 11 anti-angiogenic TKIs with different binding capacities to angiogenic receptor tyrosine kinase have been approved for the treatment of patients with advanced cancers. This review presents all approved anti-angiogenic small molecule receptor TKIs so far with an emphasis on their indications and clinical efficacy. We also discuss the combination between TKIs and immune checkpoint blockade inhibitors based on the most recent exciting outcome in immunotherapy.