BackgroundAbdominal primary Ewing sarcoma (ES) is extremely rare and carries a dismal prognosis when metastatic. First-line therapy typically involves multi-agent regimens like VDC/IE, with irinotecan-based combinations reserved for relapsed/refractory disease. This case is unique due to the achievement of long-term survival using first-line irinotecan and cisplatin in a patient with aggressive abdominal ES.Case presentationA 25-year-old female presented initially with hematochezia, and a huge abdominal mass after postoperative pathology confirmed a diagnosis of high-grade ES/PNET with rapid postoperative progression with new splenic metastases and regional lymph node involvement (no pulmonary metastases). Owing to factors related to treatment tolerance, she received an individualized treatment approach consisting of irinotecan plus cisplatin combined chemotherapy. Serial tumor response assessments demonstrated continuous reduction, culminating in a complete response (CR) that has been maintained to the present. The progression-free survival (PFS) has reached 76 months, representing a significant achievement in terms of long-term, high-quality survival.ConclusionThis case suggests that for selected patients with advanced ES, a regimen of irinotecan plus cisplatin may be considered as a potential first-line option. Larger studies are needed to validate these findings.

Biliary tract cancer (BTC) is an uncommon and aggressive neoplasm, with most patients presenting in an advanced stage. Systemic chemotherapy is the limited treatment available but is unsatisfactory, while targeted therapy is still awaiting validation from clinical trials. Given the potential effect of immune checkpoint inhibitors (ICIs) in the treatment of BTC, this review aims to summarize the evidence-based benefits and predictive biomarkers for using inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) ligand, or programmed cell death protein-1 and its ligand (PD-1 and PD-L1) as monotherapy or combined with other anti-tumor therapies, while also pointing out certain pitfalls with the use of ICIs which need to be addressed.

Background: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third-or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8-11 months in the West and 13-17 months in East Asia/ Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. Methods/Design: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). Discussion: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy.

Background: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8–11 months in the West and 13–17 months in East Asia/ Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. Methods/Design: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). Discussion: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. Trial Registration: ChiCTR.gov.cn: ChiCTR2000034109.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. Circular RNAs (circRNAs) are recently identified as important gene regulators with critical roles in cancer biology. In this study, we focus on the effect of circ_0000376 targeting miR-384 on malignant phenotypes of NSCLC cells. METHODS: Circ_0000376 and miR-384 expression in NSCLC tissue samples were measured using qRT-PCR. The association between pathological parameters and the circ_0000376 expression was analyzed as well. Human NSCLC cell lines A549 and NCI-H460 were used as cell models. CCK-8 and BrdU assay were used to assess the effect of circ_0000376 on NSCLC cell line proliferation and drug sensitivity. Transwell assay was conducted to detect the effect of circ_0000376 on migration and invasion. Further, luciferase reporter assay was employed to validate the targeting of miR-384 by circ_0000376. RESULTS: Circ_0000376 expression in NSCLC clinical samples was up-regulated and this was linked to unfavorable pathological parameters. Circ_0000376 markedly accelerated the proliferation and metastasis, and enhanced chemoresistance of NSCLC cells. Mechanically, circ_0000376 overexpression could bind with miR-384 and repress its expression. CONCLUSIONS: Circ_0000376 is a newly discovered oncogenic circRNA in NSCLC, and can be potentially regarded as a diagnostic biomarker and therapy target.

This study aimed to investigate the effect and mechanism of long non-coding RNA FLVCR1-AS1 on proliferation, invasion and migration of colorectal cancer. QRT-PCR was used to detect the expression of FLVCR1-AS1 in colorectal cancer. The target genes of FLVCR1-AS1 were predicted using the StarBase and Luciferase assay. The biological function of miR-493-3p through a series of in vitro experiments. We examined the expression of FLVCR1-AS1 in colorectal cancer cell lines was remarkably increased. Interference with FLVCR1-AS1 inhibits proliferation, invasion and migration of colorectal cancer cell lines. MiR-493-3p is a targeted miRNA of lncRNA FLVCR1-AS1, and overexpression of miR-493-3p inhibits proliferation of colorectal cancer cells, invasion and migration of colorectal cancer cells, and it can be reversed by lncRNA FLVCR1-AS1. LncRNA FLVCR1-AS1 acts as miR-493-3p sponge to modulate cancer cell proliferation, invasion and migration in colorectal cancer.

Objective:To investigated the associations between genetic polymorphisms of three genes involved in DNA repair and clinical outcomes in MGC patients receiving XELOX treatment.Methods:This retrospective study in-cluded 100 Chinese MGC patients receiving XELOX as first-line chemotherapy.Six single nucleotide polymorphisms (SNPs)of three genes (ERCC1 rs11615,ERCC2 rs13181 and rs1799793,and XRCC1 rs25487,rs25489,and rs1799782)were genotyped,and the associations between each SNP and clinical outcome were analyzed.Results:XRCC1 rs25487 A allele was significantly associated with progression disease (PD)to chemotherapy,and patients with GG genotype had significantly better progression-free survival (PFS)(8 months,95% CI:6.34 ~ 9.66,P <0.05)compared with patients with the G allele (AA + GA).ERCC2 rs13181 G allele was significantly associated with PD,and TT homozygotes tended to have better PFS(7.46 months,95% CI:6.45 ~ 8.48,P< 0.05)than carriers (GG + GT).ERCC2 rs13181 G/ T gene type were finally included in the COX regression model with a significance level of P< 0.05(HR = 0.72,95% CI:0.53 ~ 0.97,P = 0.025).Conclusion:These results suggest that the prognos-tic index comprising XRCC1 rs13181 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with XELOX.

Objective To investigate the effect of single nucleotide polymorphism of XRCC1Arg194Trp and Arg399Gln genes on the sensitivity of capecitabine combined with oxaliplatin as first line chemotherapy in patients with gastric cancer. Methods Eighty-six patients pathologically confirmed as advanced gastric cancer in our hospital from Jan. 2013 to Jun. 2014 were enrolled in the study, which were all treated with capecitabine combined with oxaliplatin chemotherapy. The clinical effects were evaluated after 3 cycles of treatment. The clinical data and peripheral blood sam-ples were collected, and genotyping of XRCC1Arg194Trp and Arg399Gln were performed by using TaqMan-MGB probe. Then the effects of treatment were compared between different genotypes. Results Among the 86 patients, 52 (60.5%) were sensitive to chemotherapy. At XRCC1Arg194Trp locus, the patients carrying Trp (Arg/Trp+Trp/Trp) geno-type had the sensitivity to chemotherapy of 70.8%, and the patients carrying Arg/Arg genotype had the sensitivity of 47.4%, P=0.027. The median time to progression (TTP) was 9.48 months for patients with Trp genotype and 7.36 months for those with Arg/Arg genotype, P=0.024. The risk of drug resistance for Arg/Arg genotype was significantly higher than that of Trp genotype (OR:2.84, 95%CI:0.772~4.313, P=0.031). At XRCC1Arg399/Arg locus, the patients carrying Arg/Arg genotype had the sensitivity of 72.5%, and the patients carrying Gln (Arg/Gln+Gln/Gln) genotype had the sensitivity to chemotherapy of 42.9%, P=0.007. The median TTP was 10.26 months for patients with Arg/Arg geno-type and 8.03 months for those with Gln genotype, P=0.012. The risk of drug resistance for Gln genotype was signifi-cantly higher than that of Arg/Arg genotype (OR:4.62, 95%CI:1.637~7.201, P=0.012). Conclusion Single nucleotide polymorphism of XRCC1Arg194Trp, Arg399Gln gene maybe associated with the sensitivity of capecitabine combined with oxaliplatin chemotherapy.

胰腺癌高度恶性，在西方国家中成为第四大消化道肿瘤的死因，在美国更是位列第二位，国内胰腺癌发病率也有逐渐增高的趋势。有研究显示，胰腺癌在确诊后5年生存率小于5%［1］。目前医学界对胰腺癌相关基因已经有了深入的研究，笔者就与胰腺癌发生、发展相关的癌基因进行了综述。

目的 比较血清肿瘤标志物联合检测在贲门癌及胃窦癌诊断中阳性率的差异,探讨其临床应用价值. 方法 选择2010-12 ～2014-03就诊于我院并且资料完整的212例胃癌患者进行研究,根据其癌症部位分为胃窦癌组和贲门癌组,并以200例健康体检病人作为正常对照组进行分析.比较三种血清肿瘤标志物血清癌胚抗原(CEA)、糖类抗原72-4(CA72-4)以及糖类抗原19-9(CA19-9)单独检测以及联合检测对贲门癌及胃窦癌诊断阳性率的影响. 结果 单独检测3种肿瘤标志物对贲门癌和胃窦癌的阳性率经统计学分析差异无统计学意义(P＞0.05);而联合肿瘤标志物进行检测时,CA72-4联合CA19-9检测对其阳性率影响不大(P＞0.05),但CEA的联合检测阳性率明显提高,胃窦癌组三者联合检测的阳性率可高达72.90％,而贲门癌组三者联合检测的阳性率也可达58.10％,差异有统计学意义(P＜0.05). 结论 血清CEA、CA72-4以及CA19-9水平在贲门癌及胃窦癌的诊断上具有一定的临床意义,联合检测可显著提高胃癌尤其是胃窦癌的诊断阳性率,其结果优于单独检测,值得在临床上推广使用.