Spinal cord biological safety of image-guided radiation therapy versus conventional radiation therapy

Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.

The Characteristics of Celiac Trunk Lymph-node Metastases of Esophageal Cancer in the Thoracic Segment and Clinical Significance for Wide-Excision

OBJECTIVE To understand the characteristics of celiac trunk lymph-node metastases of thoracic esophageal carcinoma and their influence on prognosis of the patients, and to investigate a reasonable range for regional celiac trunk lymph-node clearance. METHODS Clinical specimens of 241 patients receiving resection of a thoracic esophageal carcinoma were analyzed retrospectively. RESULTS The rate of the patient celiac lymph-node metastases was 32.4%(78/241), and of the lymph nodes examined, 9.8% were found to have metastasis. The extent of metastases adjacent to the common hepatic artery and celiac trunk and within the hepatoduodenal ligaments was 6.6%, 6.9% and 6.3%, respectively. The tumor site, extent of invasion and level of cell differentiation were the factors influencing lymph-node metastases, but they were unrelated to the length of the tumor. The overall rate of regional celiac recurrence for the patients 3 years after operation was 5.4%. The 3-year survivals for the patients with metastases of the celiac lymph nodes was 42.3%, which was lower compared to the non-metastatic patients (70.6%) (P<0.01). CONCLUSION Celiac lymph-node metastases are one of key factors affecting the prognosis of the patients receiving resection of esophageal cancer, and extensive clearance of the celiac-trunk lymph nodes can reduce the rate of postoperative regional metastases.

Prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer from multiple centers in China

AIM To explore the features and prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer(CRC).METHODS In all,321 cases of T1-stage CRC were selected from 10132 patients with CRC who received surgical therapy in six large-scale hospitals in China and were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for lymphatic metastasis. A survival analysis was then performed to analyze the prognostic value of lymph node metastasis.RESULTS The occurrence rate of T1 stage was 3.17%(321/10132);of these patients,the lymph node metastasis rate was 8.41%(27/321),and the non-lymph node metastasis rate was 91.59%(294/321). Univariate analysis showed that preoperative serum CEA,preoperative serum CA199,preoperative serum CA724,vascular invasion,and degree of differentiation were associated with lymph node metastasis in T1-stage CRC(P < 0.05 for all). Multivariate analysis indicated that preoperative serum CA724,vascular invasion,and degree of differentiation were closely related to lymph node metastasis(P < 0.05 for all). Log-rank survival analysis showed that age,preoperative serum CEA,preoperative serum CA199,vascular invasion,degree of differentiation,and lymph node metastasis(χ2 = 24.180,P < 0.001) were predictors of 5-year overall survival(OS)(P < 0.05 for all). COX regression analysis demonstrated that preoperative serum CA199 and lymph node metastasis(HR = 5.117;P < 0.05;95%CI: 0.058-0.815) were independent prognostic indicators of 5-year OS in patients with T1-stage CRC(P < 0.05 for both). CONCLUSION The morbidity of T1-stage CRC was 3.17% for all CRC cases. Preoperative serum CA724,vascular invasion,and degree of differentiation are independent risk factors for lymph node metastasis. Lymph node metastasis is an independent prognostic factor for OS in patients with T1-stage CRC.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Jinlong capsule decreases adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma

Objective The aim of this study was to analyze whether Jinlong capsule could decrease adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma. Methods Eighty-two patients with hepatocellular carcinoma were randomly divided into the control group and experimental group. On the first day after TACE, the experimental group started receiving four Jinlong capsules orally three times daily, whereas the control group did not receive the treatment.Results The incidences of erythropenia and thrombocytopenia in the experimental group was lower than those in the control group(P = 0.040 and 0.033, respectively). The differences in serum levels of aminotransferase, albumin, potassium, and sodium between the two groups were significant(P = 0.034, 0.034, 0.013, and 0.044, respectively). The mean durations of stomachache and abdominal distension in the experimental group was significantly shorter than those in the control group(P = 0.004 and 0.021, respectively). However, there were no significant differences in the incidences of nausea, fever, and vomiting between the two groups(P = 0.490, 0.495, and 0.585, respectively). Conclusion The reduction in the incidence rate and duration of partial adverse reactions after TACE was observed in hepatocellular carcinoma patients treated with Jinlong capsule compared to untreated patients, suggesting possible beneficial effects exerted by Jinlong capsule on the reduction of TACE-induced liver damage, thereby improving liver function and, consequently, the quality of life.

HLA-A*02-B*46 Haplotype: an Adverse Prognostic Factor in Han Patients with Nasopharyngeal Carcinoma

Epidemiological studies have shown that human leukocyte antigen（HLA） allelic polymorphisms are closely correlated to susceptibility to nasopharyngeal carcinoma（NPC）, and in a previous study, we showed that HLA-B＊46 and HLA-A＊02-B＊46 haplotypes were strongly associated with NPC susceptibility. In this retrospective study, we investigated the phenotype of the HLA-A and HLA-B alleles and haplotypes and correlated these data to the clinical and pathological parameters of NPC to understand the role of HLA alleles and haplotypes in NPC prognosis. The cohort comprised 117 NPC patients from a Han population in Xinjiang. The local recurrence-free survival（LRFS）, distant metastasis-free survival（DMFS）, disease-free survival（DFS）, and overall survival（OS） were analyzed. The 5-year DMFS of the HLA-A＊02-B＊46 haplotype carriers and non-carriers was 66.4% and 90.3%, respectively. In addition, age was found to be a prognostic factor for LRFS, DFS, and OS（P=0.032, 0.040, and 0.013, respectively）. We found that the HLA-A＊02-B＊46 haplotype might be a prognostic marker in addition to the traditional TNM staging in patients with NPC.

UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway

Background:Ubiquitin-conjugating enzyme E2C(UBE2C)has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes.This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer(BC)proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.Then differentially expressed genes(DEGs)were identified using Venn diagram analysis.By using DEGs,we conducted the following analyses including Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein-protein interaction(PPI),and survival analysis,and then validated the function of the hub geneUBE2C using quantitative reverse transcription-polymerase chain reaction(RT-qPCR),cell counting kit-8(CCK-8)assay,transwell assay,and Western blot assay.Results:In total,151 DEGs were identified from the GEO and TCGA databases.The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division,lipid droplet,and organic acid-binding.KEGG analysis showed that the peroxisome proliferators-activated receptor(PPAR)signaling pathway,regulation of lipolysis in adipocytes,and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category.The top three hub genes that resulted from the PPI network wereFOXM1,UBE2C,andCDKN3.The results of survival analysis showed a close relationship between UBE2C and BC.The results of CCK-8 and transwell assays suggested that the proliferation and invasion ofUBE2C knockdown cells were significantly inhibited(P<0.050).The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10(p-PTEN)was obviously increased(P<0.050),whereas the levels of phosphorylated protein kinase B(p-AKT),phosphorylated mammalian target of rapamycin(p-mTOR),and hypoxia-inducible factor-1 alpha(HIF-1α)were dramatically decreased(P<0.050)in theUBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.

Association between circulating CD39+CD8+T cells prechemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma

Background:The mortality rate among patients with nasopharyngeal carcinoma(NPC)has improved significantly with the advent of chemoradiotherapy strategies.However,distant metastasis remains problematic.Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+T cells,particularly in CD39+CD103+T cells.Circulating cancer-specific T cells are important for protecting against metastasis.This study aimed to evaluate the predictive value of circulating CD39+CD8+T cells for metastasis in patients with NPC.Methods:We performed a cross-sectional,longitudinal study of 55 patients with newly diagnosed NPC of stage III–IVa.All patients were initially treated with standard combined chemoradiotherapy.Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment.T cell expression of CD39 and CD103,together with the markers of T cell exhaustion programmed death-1(PD-1)/T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA,was examined by flow cytometry.The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups.Kaplan-Meier analysis was used for analysis of progression-free survival(PFS).Results:The expression of circulating CD39+CD8+and CD39+CD103+CD8+T cells was significantly higher in patients without distant metastasis(CD39+CD8+:6.52%[1.24%,12.58%]vs.2.41%[0.58%,5.31%],Z=2.073,P=0.038 and CD39+CD103+CD8+:0.72%[0.26%,2.05%]vs.0.26%[0.12%,0.64%],Z=2.313,P=0.021).Most CD39+T cells did not express PD-1 or Tim-3.Patients with high expression of CD39+CD103+CD8+T cells had better PFS than patients with low expression(log rank value=4.854,P=0.028).CD39+CD8+T cells were significantly elevated at 1-month post-treatment(10.02%[0.98%,17.42%]vs.5.91%[0.61%,10.23%],Z=2.943,P=0.003).The percentage of advanced differentiated CD8+T cells also increased at 1-month post-treatment compared with pre-treatment(33.10%[21.60%,43.05%]vs.21.00%[11.65%,43.00%],Z=2.155,P=0.031).There was a significant correlation between elevated CD39+CD8+T cells and increased effector memory T cells(intermediate stage:r=0.469,P=0.031;advanced stage:r=0.508,P=0.019).Conclusions:CD39+CD8+circulating T cells have preserved effector function,contributing to an improved prognosis and a reduced risk of metastasis among NPC patients.These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 T Cell Response in Blood

Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.