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.

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.

Impact of crizotinib on long-term survival of ALK-positive advanced non-small-cell lung cancer: A Chinese multicenter cohort study

Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.

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.

Clinical Application of Lobaplatin Combined with Docetaxel in Adjuvant Chemotherapy for Triple-Negative Breast Cancer in Elderly Patients

To investigate the adverse reactions and efficacy of docetaxel combined with lobaplatin in adjuvant chemotherapy for triple-negative breast cancer in elderly patients.A total of 96 elderly triple-negative breast cancer patients admitted to our hospital from January 2008 to December 2011 were randomly divided into two groups.A group of 56 patients received docetaxel 75 mg·m^(-2),intravenous drip,d1;lobaplatin 30 mg·m^(-2),intravenous drip,d1;21 days repeat,a total of 6 cycles.A group of 40 patients received chemotherapy for 6 cycles with an anthracycline-containing(TEC)regimen.Comparison of adverse reactions and 5-year diseasefree survival in both groups.The incidence of thrombocytopenia was significantly higher in 56 patients with TL regimen than those with TCE-containing anthracyclines(P=0.005).But the incidence of cardiotoxicity was 32.5%in the TEC group.And the difference was statistically significant(P=0.008).The 5-year disease-free survival rate was 73.2%in the TL group and 67.5%in the TEC group.There was no statistical difference.Docetaxel combined with lobaplatin in the treatment of elderly triple-negative breast cancer has no significant difference in efficacy compared with traditional anthracycline-containing drugs,but it can avoid the cardiotoxicity caused by anthracyclines.It’s a new option for elderly TNBC adjuvant chemotherapy,suggesting to expand the sample content for further research.

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.

Human papillomavirus distribution and cervical cancer epidemiological characteristics in rural population of Xinjiang,China

Background:Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang.This study aims to investigate the distribution of human papillomavirus(HPV)infection and cervical cancer in rural areas of Xinjiang,China.Methods:Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang,China in 2017 through gynecological examination,vaginal discharge smear microscopy,cytology,and HPV testing.If necessary,colposcopy and biopsy were performed on women with suspicious or abnormal screening results.Results:Of the 216,754 women screened,15,518 received HPV testing.The HPV-positive rate was 6.75%(1047/15,518).Compared with the age 35-44 years group,the odds ratios(ORs)of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18(95%confidence interval[Cl]:1.02-1.37)and 1.84(95%Cl:1.53-2.21),respectively.Compared with women with primary or lower education level,the ORs for HPV infection rates of women with high school and college education or above were 1.37(95%Cl:1.09-1.72)and 1.62(95%Cl:1.23-2.12),respectively.Uyghur women were less likely to have HPV infection than Han women,with an OR(95%Cl)of 0.78(0.61-0.99).The most prevalent HPV types among Xinjiang women were HPV 16(24.00%),HPV 33(12.70%),and HPV 52(11.80%).The detection rate of cervical intraepithelial neoplasia(CIN)2+was 0.14%and the early diagnosis rate of cervical cancer was 85.91%.The detection rates of vaginitis and cervicitis were 19.28%and 21.32%,respectively.Conclusions:The HPV infection rate in Xinjiang is low,but the detection rate of cervical cancer and precancerous lesions is higher than the national average level.Cervical cancer is a prominent public health problem in Xinjiang,especially in southern Xinjiang.

Hypoxia-associated circular RNA RPPH1 modulates triple-negative breast cancer cell growth via the miR-1296-5p/TRIM14 axis

Hypoxia affects the advancement,metastasis,and metabolism of breast cancer(BC).The circular RNA ribonuclease P RNA component H1(circRPPH1)(has_circ_0000515)is implicated in tumor progression.Nevertheless,the regulatory mechanism related to circRPPH1 in hypoxia-mediated triple-negative breast cancer(TNBC)progression is indistinct.The expression levels of circRPPH1,miR-1296-5p,tripartite motif-containing 14(TRIM14)mRNA in tissue samples and cells were examined through quantitative real-time polymerase chain reaction(qRT-PCR).Cell viability,migration,and invasion were determined with Cell Counting Kit-8(CCK-8)or transwell assays.The levels of glucose consumption and lactate production were assessed via the Glucose Assay Kit or Lactate Assay Kit.The protein levels of TRIM14,Glucose Transporter GLUT1(GLUT1),and lactic dehydrogenase A(LDHA)were detected by western blot analysis.The targeting relationship between circRPPH1 or TRIM14 and miR-1296-5p was verified with dual-luciferase reporter assay.The role of circRPPH1 was confirmed via xenograft assay.We verified that circRPPH1 and TRIM14 expression were increased while miR-1296-5p expression was decreased in BC tissues and hypoxia-cultured TNBC cells.Functionally,circRPPH1 silencing reversed the promoting effect of hypoxia on viability,migration,invasion,and glycolysis of TNBC cells.CircRPPH1 knockdown repressed decreased TNBC cell growth in vivo.Mechanistically,circRPPH1 sponged miR-1296-5p to modulate TRIM14 expression.Also,miR-1296-5p silencing restored circRPPH1 inhibition-mediated influence on the viability,migration,invasion,and glycolysis of hypoxia-treated TNBC cells.TRIM14 elevation overturned the inhibitory impact of miR-1296-5p mimic on viability,migration,invasion,and glycolysis of hypoxia-cultured TNBC cells.In conclusion,hypoxia-induced circRPPH1 fostered TNBC progression through regulation of the miR-1296-5p/TRIM14 axis,indicating that circRPPH1 was a promising target for TNBC treatment.

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.

A New Beam Selection Method for MLC-Based Robotic Radiotherapy

Purpose: The CyberKnife system equipped with multileaf collimator (MLC) has been shown promising in treatment-time reduction and plan-quality improvement, because of the enhanced coverage of larger lesions and the improved target conformity. In this study, we aim to develop an efficient non-coplanar beam selection program for CyberKnife-based IMRT. Method: The candidate beam set in this study consists of 94 non-coplanar beams, each defined by a vector connecting a CyberKnife node and a target point. Our goal is to choose an adequately small number of beams that will allow the generation of high quality IMRT plans. We use the beam coverage of patient-surface as a surrogate for the solution space of beamlet-based inverse planning. Based on body-surface coverage and beam-projection overlap on the surface, a beam-selection program was developed. To evaluate the effectiveness of the beam selection method, IMRT plans with the selected beams for different treatment sites were generated using the Varian Eclipse treatment planning system and compared with the IMRT plans with conventional coplanar beams. Results: Our program efficiently selected a subset of relatively small number of non-coplanar beams, while pre-serving the body-surface coverage and therefore the solution space for inverse planning optimization. For example, a set of 17 beams were selected for a pancreatic cancer case, covering 92.5% of the surface area which was covered by all the 94 candidate beams with the same field size. The IMRT plans with the selected beams show superior quality with dramatically improved critical structure sparing, as compared with the clinically approved IMRT plans. Conclusion: One can efficiently select effective sets of non-coplanar beams with our program, which allow the generation of high-quality plans for MLC-based robotic radiotherapy.

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.

A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer

Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular emboliza-tion could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.Methods:A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system.The internal validation was analyzed by bootstrap-corrected C-indexes(resampled 1000 times).Data from 436 patients who were treated at 15 centers over four conti-nents were used for external validation.Results:A survivorship overlap was observed between T2 and T3 patients(P=0.587)classified according to the 8th AJCC-TNM staging system.Lymphovascular embolization was a significant prognostic factor for metastasis and survival(all P<0.001).Based on the multivariate analysis,only lymphovascular embolization showed a significant influ-ence on cancer-specific survival(CSS)(hazard ratio=1.587,95%confidence interval=1.253-2.011;P=0.001).T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascu-lar embolization(P<0.001).Therefore,a modified clinicopathological staging system was proposed,with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows:t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion,and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion.The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories(all P<0.005)and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system(C-index,0.739 vs.0.696).These results were confirmed in the external validation cohort.Conclusions:T2-3 penile cancers are heterogeneous,and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system.

Predicting late radiation-induced xerostomia in nasopharyngeal carcinoma based on radiomics features extracted from T2WI images of parotids

Objective:To explore the value of radiomics features extracted from the T2-weighted imaging(T2WI)images of parotids in predicting late radiation-induced xerostomia in nasopharyngeal carcinoma(NPC)patients after radiotherapy(RT).Methods:A retrospective analysis was conducted for 123 NPC patients who received RT at the Affiliated Tumour Hospital of Xinjiang Medical University from January 2019 to March 2021.All the patients underwent MRI pre-RT and post-RT.They were randomly divided into a training set and a testing set at a ratio of 4:1 using a random number table,with the former and the latter comprising 98 and 25 cases,respectively.The ipsilateral parotid gland(iPG)and the contralateral parotid gland(cPG)were delineated on T2WI images pre-RT and post-RT as regions of interest(ROIs).A total of 851 radiomics features were extracted from each ROI.Spearman analysis was used to remove redundant features,and the recursive feature elimination(RFE)method was then used to determine useful features.Using radiomics features extracted from images pre-treatment,images post-treatment,and differences between images pre-and post-treatment,this study constructed three radiomic models,namely the pre-treatment radiomics model(preRT),the post-treatment radiomics model(postRT),and the deltaradiomics model(DeltaRT).Then,this study plotted the receiver operating characteristic(ROC)curves based on the late radiation-induced xerostomia grades of patients post-RT.Furthermore,the models’effectiveness and performance in predicting late radiation-induced xerostomia and advanced radioactive xerostomia was evaluated.In addition,the area under the curve(AUC),sensitivity,specificity,accuracy,precision,and negative predictive value(NPV)were calculated.Results:Among the features extracted from bilateral parotid glands(PGs),20 were determined pre-RT(six from iPG and 14 from cPG),19 were determined post-RT(six from iPG and 13 from cPG),and 20 were derived from the DeltaRT(20 from cPG).The PGs pre-RT and post-RT in the training set had AUCs of 0.902(95%CI:0.895-0.909)and 0.761(95%CI:0.744-0.778),respectively,while those in the testing set had AUCs of 0.740(95%CI:0.504-0.983)and 0.701(95%CI:0.478-0.924),respectively.In contrast,the AUC of the cPG derived from the DeltaRT was 0.867(95%CI:0.856-0.878)in the training set and 0.851(95%CI:0.697-0.999)in the testing set.Conclusions:There are significant correlations between radiomics features extracted from MRI T2WI images of parotids and late radiation-induced xerostomia in NPC patients.Among the radiomics features,the changes in cPG features pre-RT and post-RT have higher accuracy in predicting late radiation-induced xerostomia.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial

Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.

Detection of breast cancer based on novel porous silicon Bragg reflector surface-enhanced Raman spectroscopy-active structure

In this Letter, the surface-enhanced Raman scattering(SERS) signal of early breast cancer(BRC) patient serum is obtained by a composite silver nanoparticles(Ag NPs) PSi Bragg reflector SERS substrate. Based on these advantages, the serum SERS signals of 30 normal people and 30 early BRC patients were detected by this substrate. After a baseline correction of the experimental data, principal component analysis and linear discriminant analysis were used to complete the data processing. The results showed that the diagnostic accuracy, specificity,and sensitivity of the composite Ag NPs PSi Bragg reflector SERS substrate were 95%, 96.7%, and 93.3%, respectively. The results of this exploratory study prove that the detection of early BRC serum based on a composite Ag NPs PSi Bragg reflector SERS substrate is with a stable strong SERS signal, and an unmarked and noninvasive BRC diagnosis technology. In the future, this technology can serve as a noninvasive clinical tool to detect cancer diseases and have a considerable impact on clinical medical detection.

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.

Nasopharyngeal brushing: a convenient and feasible sampling method for nucleic acid-based nasopharyngeal carcinoma research

Background:Tissue specimens for nasopharyngeal carcinoma(NPC)research are scarce because of sampling dif-ficulties.Previous studies have suggested non-invasive nasopharyngeal brushing as an effective sampling method for NPC diagnosis.The present study aimed to evaluate the feasibility of nasopharyngeal brushing in the acquisition of NPC nucleic acids for research.Methods:Nasopharyngeal brushing samples were acquired from 24 healthy individuals and 48 NPC patients.Tissues from 48 NPC and 18 nasopharyngitis patients were collected by endoscopic biopsy.The expression levels of tumor suppressor genes(TSGs)and Epstein-Barr virus(EBV)-encoded microRNAs as well as EBV DNA copy number were measured by quantitative polymerase chain reaction in both types of samples.Results:Among six TSGs examined,the expression levels of two genes were significantly decreased in nasopharyn-geal brushing and tissue samples from NPC patients as compared with those from healthy/nasopharyngitis indi-viduals.Four EBV-encoded microRNAs,mir-bart1-5p,mir-bart5,mir-bart6-5p,and mir-bart17-5p,were significantly up-regulated in both NPC brushing and tissue samples compared with those from healthy/nasopharyngitis controls(P<0.001).EBV DNA was significantly increased in both nasopharyngeal brushing samples(P<0.001)and tissue sam-ples(P<0.001)from NPC patients in comparison with those from healthy controls.Conclusions:Nasopharyngeal brushing can obtain sufficient tumoral materials for the analysis of viral nucleic acid,including EBV-encoded microRNAs and EBV DNA.For the detection of TSG expression,nasopharyngeal brushings was feasible but inferior to tissue samples.This study confirms nasopharyngeal brushing as an applicable sampling method that can aid in nucleic acid-based NPC research.

Well-differentiated systemic mastocytosis with KIT K509I mutation and uterus infiltration in an Asian woman with good response to imatinib

To the Editor: We report a 27-year-old woman with a 2-month history of irregular uterine bleeding between periods. Blistering on the head was noted in the patient at the age of 2 months, and she gradually developed red maculopapular lesions over her neck and back during puberty, which were itchy after exposure to physical friction. On admission, physical examination had revealed diffuse faint maculopapular rash mainly on the neck and back [Figure 1]. Pelvic examination showed a smooth red lump (5 cm) on the cervix. No abnormality was detected in the complete blood count. Afterwards, the cervical lump was resected and confirmed to be the infiltration of mature mast cells (MCs) after careful pathological investigation. Additionally, a skin nodule biopsy also indicated mass aggregation of MCs, and a bone marrow (BM) biopsy showed a mass of round MCs with abundant cytoplasmic granules. The MCs accounted for about 22.5% of all cells in the aspirate smears. Flow cytometry immunophenotypic analysis on BM suggested that an aberrant MC population had represented 10% of the total analyzed cells, which was positive for CD117, CD33, and CD9, partially positive for CD2 and CD68, and negative for CD25. Genetic test through exome-wide sequencing for the receptor tyrosine kinase (KIT) gene had revealed K509I mutation.