Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.

Colorectal cancer of the young displays distinct features of aggressive tumor biology:A single-center cohort study

BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies.AIM To study tumor biology in CRC patients below 50 years of age.METHODS All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age(≥50 and<50 years).Clinical as well as histopathological features were analyzed and compared.The study was approved by the local Ethics Committee.Fisher’s exact test or t-test was used to test for differences between the groups,as appropriate.All statistical analysis was performed with IBM SPSS software Version 25(SPSS Inc,Armonk,NY,United States)and with RStudio using R Version 3.4.1(RStudio,Boston,MA,United States).RESULTS Seventeen percent of the 411 patients were younger than 50 years.Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases(36.6%and 62%vs 17.7%and 42%;P<0.01).In addition,a higher frequency of poorly differentiated(G3)tumors(40%vs 22.4%P<0.05)was observed.More than every second patient below 40 years of age(51.8%)had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients≥50 years(14.8%,P<0.05).Mutational status(KRAS,NRAS,BRAF,MSI)as well as selected behavioral risk factors showed no significant differences.CONCLUSION Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset.Those patients present more frequently with more advanced tumor stages compared to older patients.Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.

Efficacy of vinorelbine combined with low-dose methotrexate for treatment of inoperable desmoid tumor and prognostic factor analysis

Objective： To assess the efficacy of conservative chemotherapy for inoperable desmoid tumor（DT） and analyze the prognostic factors.Methods：From November 2008 to April 2016,71 patients of inoperable DT were treated with vinorelbine and low-dose methotrexate in the Department of Bone and Soft Tissue Tumors,Peking University Cancer Hospital＆Institute,and enrolled in this retrospective study.The chemotherapy duration is one year.The efficacy of chemotherapy and the prognosis were observed.Results：Of the 71 patients,55% were female.Age of onset varied from 1 to 47 years,and the median age was 14years.Only 11（15.5%）cases suffered primary tumor.The distribution of the site of tumors was：31（43.7%）in the trunk,36（50.7%）in the limbs,and 4（5.6%）in the peritoneal and pelvic cavity.The size of tumor（the maximum diameter）differed from 2 to 37 cm with a mean of 9.3 cm.The median follow-up duration was 28（range,6–87）months.Common side effects included：nausea and vomiting,liver injury,bone marrow suppression and oral ulcers.When the chemotherapy finished,1（1.4%）case achieved complete response,24（33.8%）achieved partial response,37（52.1%）achieved stable disease and 9（12.7%）had progressive disease.The overall response rate was 87.3%.The progression-free survival（PFS）of the participants were from 6 to 87 months,and the 2-,3-and 5-year PFS was 79.9%,68.4% and 36.3%,respectively.No significant difference was identified in PFS in subgroups of gender,age of onset,age of chemotherapy,tumor site and tumor size.Conclusions：For recurrent,inoperable and progressive DT,enough course of chemotherapy with vinorelbine combined with low-dose methotrexate was an optional choice for local control.