A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk nonmuscle-invasive bladder cancer

Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Bilirubin inhibits the anticancer activity of sorafenib by blocking MCL-1 degradation in hepatocellular carcinoma cells

Objective:Sorafenib is a first-line drug for advanced hepatocellular carcinoma(HCC).Unfortunately,most patients with HCC do not respond to sorafenib,mainly because of the frequent development of drug resistance.Bilirubin is an end metabolite of heme catabolism and an indicator of liver function,but its direct role in regulating the anticancer activity of sorafenib in HCC cells is unclear.In the current study,we aimed to investigate the mechanism of action of bilirubin in sorafenib-mediated tumor suppression in HCC.Methods:A retrospective observational cohort of 100 patients receiving sorafenib was conducted to evaluate the potential role of bilirubin in predicting the prognosis of patients with HCC.Human HCC cell lines were treated with sorafenib in the absence or presence of bilirubin,and cell proliferation,apoptosis,and signaling pathways were assayed.The antagonistic effect of bilirubin toward sorafenib was assessed in nude mice bearing HCC xenografts.Results:Serum levels of bilirubin(including total,direct,and indirect bilirubin)negatively correlated with the overall survival of patients with HCC treated with sorafenib(P<0.05).Both in vitro and in vivo analyses demonstrated that bilirubin significantly abrogated sorafenib-mediated proliferation inhibition and apoptosis induction in HCC cells(P<0.05).Mechanically,bilirubin inhibited sorafenib-induced activation of GSK-3βand subsequent downstream MCL-1 degradation.Conclusions:Our study provides experimental evidence of the antagonistic effect of bilirubin toward sorafenib-mediated anticancer activity in HCC,and it suggests that bilirubin could be used to predict the efficacy of sorafenib treatment.

Effect and Significance of Comprehensive Training in Infection Prevention and Control on the Psychological Health of Oral Health Staff

Background:Oral health staff have close contact with patients in the process of diagnosis and treatment,and it is inevitable for them to come into contact with patients’secretions.Therefore,oral health staff are at greater risk of infectious diseases in their daily work,and their psychological health is also greatly challenged.Objective:To study the effect and significance of comprehensive training in infection prevention and control on the psychological health of oral health staff.Methods:We selected 400 oral health staff from a tertiary stomatological hospital in Guangzhou,China in this study.The respondents were randomly divided into an intervention group and a control group.After the first round of investigation,the intervention group received comprehensive training in prevention and control of infection for three months,while the control group received no intervention.Results:The comprehensive training in infection prevention and control improved the respondents’psychological health and job satisfaction.Further strengthening infection prevention and control training for oral health staff will increase their self-confidence,improve their mental health,and increase their job satisfaction.Conclusion:For oral health staff,it is particularly important to formulate an effective and operable preventive and control training program and then implement it in a standardized manner.

Prognostic impact of D2-plus lymphadenectomy and optimal extent of lymphadenectomy in advanced gastric antral carcinoma: Propensity score matching analysis

Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gastrectomy for advanced gastric antral carcinoma.Methods: A total of 203 patients with advanced gastric cancer(GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index(TVI) was calculate to evaluate the survival benefit of dissecting each LN station.Results: Of 102 patients with D2-plus lymphadenectomy, 21(20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival(OS) was significantly better in the D2-plus than the D2 group(P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy(hazard ratio, 0.516;P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, p N stage [odds ratio(OR), 2.533;95% confidence interval(95% CI), 1.368-4.691;P=0.003] and extent of LNs metastasis(OR, 5.965;95% CI, 1.335-26.650;P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1(No. 8p), 5.7(No. 12p), 5.1(No. 13), and 7.1(both No. 16a2 and No. 16b1), respectively.Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis:A multicenter propensity scorematched cohort study

Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.

Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients

Objective:Circulating cell-free Epstein-Barr virus(EBV)DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma(NPC).Despite important insights into the biology of persistence,few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells(PBCs).Methods:A prospective observational cohort study was conducted involving 1,063 newly diagnosed,locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007.Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival(OS)and other prognostic outcomes.Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.Results:After a median follow-up of 108 months,patients with higher PBC EBV-DNA loads had significantly worse OS[hazard ratio(HR)of medium,medium-high,and high vs.low were 1.50,1.52,and 1.85 respectively;Ptrend<0.001].Similar results were found for progression-free survival and distant metastasis-free survival.The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66,respectively.Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker,which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort(HR:1.88;P=0.025).Importantly,a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.Conclusions:The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.

Validation of different personalized risk models of chemotherapy-induced nausea and vomiting:results of a randomized,double-blind,phase III trial of fosaprepitant for cancer patients treated with high-dose cisplatin

Background:Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis.The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting(CINV)in patients with solid malignant tumors,determine risk factors and externally validate different personalized risk models for CINV.Methods:This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy.The primary endpoint was complete response(CR)during the overall phase(OP)with a non-inferiority margin of 10.0%.Logistic regression modelswere used to assess the risk factors ofCRand no nausea.To validate the personalized risk models,the accuracy of the risk scoring systems was determined by measuring the specificity,sensitivity and area under the receiver operating characteristic(ROC)curve(AUC),while the predictive accuracy of the nomogram was measured using concordance index(C-index).Results:A total of 720 patients were randomly assigned.CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group(78.1%vs.77.7%,P=0.765)with a between-group difference of 0.4%(95%CI,-5.7%to 6.6%).Female sex,higher cisplatin dose(≥70 mg/m2),no history of drinking and larger body surface area(BSA)were significantly associated with nausea.The AUC for the acute and delayed CINV risk indexes was 0.68(95%CI:0.66-0.71)and 0.66(95%CI:0.61-0.70),respectively,and the C-index for nomogram CINV prediction was 0.59(95%CI,0.54-0.64).Using appropriate cutoff points,the three models could stratify patients with high-or low-risk CINV.No nausea and CR rate were significantly higher in the low-risk group than in the high-risk group(P<0.001).Conclusions:Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy.Female cancer patients without a history of alcohol consumption,with larger BSA and received high-dose cisplatin might be more vulnerable to CINV.Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.

The suppression of cervical cancer ferroptosis by macrophages:The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types.Tumor-associated macrophages(TAMs)play a key role in promoting tumor malignant progression and therapy resistance.However,the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic.This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo.TAMs have been found to suppress cervical cancer cells ferroptosis.Mechanistically,macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells.In cancer cells,miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis.Moreover,the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway.Importantly,in clinical cervical cancer cases,ALOX15 is negatively associated with macrophages infiltration,which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer.Moreover,both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer.Altogether,this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

Omics-based integrated analysis identified ATRX as a biomarker associated with glioma diagnosis and prognosis

Objective:ATRX is a multifunctional protein that is tightly regulated by and implicated in transcriptional regulation and chromatin remodeling.Numerous studies have shown that genetic alterations in ATRX play a significant role in gliomas.This study aims to further determine the relationship between ATRX and glioma prognosis and identify possible mechanisms for exploring the biological significance of ATRX using large data sets.Methods:We used The Cancer Genome Atlas(TCGA)database and 130 immunohistochemical results to confirm the difference in ATRX mutations in high-and low-grade gliomas.An online analysis of the TCGA glioma datasets using the cBioPortal platform was performed to study the relationship between ATRX mutations and IDH1,TP53,CDKN2 A and CDKN2 B mutations in the corresponding TCGA glioma dataset.In combination with clinical pathology data,the biological significance of the relationships were analyzed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses and annotations of all adjacent genes in the network were performedin the Database for Annotation,Visualization and Integrated Discovery(DAVID)and R language.A protein-protein interaction(PPI)network was constructed,and the interactions of all adjacent nodes were analyzed by the String database and using Cytoscape software.Results:In the selected TCGA glioma datasets,a total of 2,228 patients were queried,21%of whom had ATRX alterations,which co-occurred frequently with TP53 and IDH1 mutations.ATRX alterations are associated with multiple critical molecular events,which results in a significantly improved overall survival(OS)rate.In low-grade gliomas,ATRX mutations are significantly associated with multiple important molecular events,such as ZNF274 and FDXR at mRNA and protein levels.A functional cluster analysis revealed that these genes played a role in chromatin binding and P53,and a link was observed between ATRX and IDH1 and TP53 in the interaction network.ATRX and TP53 are important nodes in the network and have potential links with the blood oxygen imbalance.Conclusions:ATRX mutations have clinical implications for the molecular diagnosis of gliomas and can provide diagnostic and prognostic information for gliomas.ATRX is expected to serve as a new therapeutic target.

Overexpression of amplified in breast cancer 1 (AIB1) gene promotes lung adenocarcinoma aggressiveness in vitro and in vivo by upregulating C-X-C motif chemokine receptor 4

Background:We previously found that overexpression of the gene known as amplified in breast cancer 1(AIB1)was associated with lymph node metastasis and poor prognosis in patients with lung adenocarcinoma.However,the role of AIB1 in that malignancy remains unknown.The present study aimed to investigate the function of AIB1 in the process of lung adenocarcinoma cell metastasis.Methods:A series of in vivo and in vitro assays were performed to elucidate the function of AIB1,while real-time PCR and Western blotting were utilized to identify the potential downstream targets of AIB1 in the process of lung adenocarcinoma metastasis.Rescue experiments and in vitro assays were performed to investigate whether the invasive-ness of AIB1-induced lung adenocarcinoma was mediated by C-X-C motif chemokine receptor 4(CXCR4).Results:The ectopic overexpression of AIB1 in lung adenocarcinoma cells substantially enhanced cell migration and invasive abilities in vitro and tumor metastasis in vivo,whereas the depletion of AIB1 expression substantially inhibited lung adenocarcinoma cell migration and invasion.CXCR4 was identified as a potential downstream target of AIB1 in lung adenocarcinoma.The knockdown of AIB1 greatly reduced CXCR4 gene expression at both the transcription and protein levels,whereas the knockdown of CXCR4 in cells with AIB1 ectopic overexpression diminished AIB1-induced migration and invasion in vitro and tumor metastasis in vivo.Furthermore,we found a significant positive association between the expression of AIB1 and CXCR4 in lung adenocarcinoma patients(183 cases),and the co-overexpression of AIB1 and CXCR4 predicted the poorest prognosis.Conclusions:These findings suggest that AIB1 promotes the aggressiveness of lung adenocarcinoma in vitro and in vivo by upregulating CXCR4 and that it might be usable as a novel prognostic marker and/or therapeutic target for this disease.

The dual role of ferroptosis in pancreatic cancer: a narrative review

Pancreatic ductal adenocarcinoma is the main cause of cancer-related mortality,with a lack of effective treatments and overall survival rates far lower than other solid cancers.This clinical challenge is related to late diagnosis as well as primary or acquired resistance to therapy-induced apoptosis.Targeting nonapoptotic cell death pathways may provide alternative therapeutic strategies to overcome drug resistance.In particular,recent studies have suggested that ferroptosis,a type of iron-dependent nonapoptotic cell death,is a promising target for pancreatic ductal adenocarcinoma.Ferroptosis can be triggered by inhibiting or activating the redox or iron metabolism-related pathways,mediated by extrinsic/membrane transports(e.g.,solute carrier family 7 member 11)or intrinsic/enzymes(e.g.,glutathione peroxidase 4).Although the exact effector molecule remains obscure,reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage appears to play a central role in mediating ferroptotic death.While treatment-induced ferroptosis is beneficial to suppress tumor growth,inflammation-related immunosuppression caused by ferroptotic damage may promote the occurrence of pancreatic ductal adenocarcinoma.In this review,we outline the latest knowledge about the regulation and function of ferroptosis in pancreatic tumorigenesis and therapy.

Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues

Although the function of tRNAs in the translational process is well established,it remains controversial whether tRNA abundance is tightly associated with translational efficiency(TE)in mammals.Moreover,how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed.Here,we measured both tRNA expression using demethylase-tRNA sequencing(DM-tRNA-seq)and TE of mRNAs using ribosome-tagging sequencing(RiboTag-seq)in the brain,heart,and testis of mice.Remarkable variation in the expression of tRNA isodecoders was observed among different tissues.When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons,we observed an expected reduction in the variation of anticodon expression across all samples,an unexpected smaller variation of anticodon usage bias,and an unexpected larger variation of tRNA isotype expression at amino acid level.Regardless of whether or not they share the same anticodons,the isodecoders encoding the same amino acids are co-expressed across different tissues.Based on the expression of tRNAs and the TE of mRNAs,we find that the tRNA adaptation index(tAI)and TE are significantly correlated in the same tissues but not between tissues;and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues.We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms.This study provides a resource for tRNA and translation studies,as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.

Bcl-3 promotes Wnt signaling by maintaining the acetylation ofβ-catenin at lysine 49 in colorectal cancer

Wnt/β-catenin signaling plays a critical role in colorectal cancer(CRC)tumorigenesis and the homeostasis of colorectal cancer stem cells(CSCs),but its molecular mechanism remains unclear.B-cell lymphoma 3(Bcl-3),a member of the IκB family,is overexpressed in CRC and promotes tumorigenicity.Here,we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/β-catenin signaling.Silencing Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/β-catenin signaling.Moreover,our data show that Bcl-3 is a crucial component of Wnt/β-catenin signaling and is essential forβ-catenin transcriptional activity in CRC cells.Interestingly,Wnt3a increases the level and nuclear translocation of Bcl-3,which binds directly toβ-catenin and enhances the acetylation ofβ-catenin at lysine 49(Ac-K49-β-catenin)and transcriptional activity.Bcl-3 depletion decreases the Ac-K49-β-catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups fromβ-catenin,thus interrupting Wnt/β-catenin activity.In CRC clinical specimens,Bcl-3 expression negatively correlates with the overall survival of CRC patients.A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-β-catenin.Collectively,our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-β-catenin,which serves as a promising therapeutic target for CRC.

A systematic review of phytochemicals from Chinese herbal medicines for non-coding RNAs-mediated cancer prevention and treatment:From molecular mechanisms to potential clinical applications

Worldwide,cancer is a growing epidemic that results in large social and economic burdens.Despite advances in current diagnosis and treatment,most of the prognosis in cancer patients remains poor.It is urgent to find alternative therapies with effective cancer prevention and treatment.Chinese herbal medicines(CHMs)have been increasingly used worldwide for cancer prevention and treatment due to their privileged properties.CHMs are useful in the suppression of various types of cancers through different mechanisms of action.Non-coding RNAs(ncRNAs),including microRNAs,long non-coding RNAs and circular RNAs,are closely involved in the cancer progression and development.Regulation of ncRNAs in tumor cells may be a useful pharmacological strategy for the cancer prevention and treatment.Substantial evidence exists that various phytochemicals from CHMs exert potent anticarcinogenic effects by regulating ncRNAs-related targets and signaling pathways.Herein,the purpose of this paper is to conclude the current understanding of phytochemicals from CHMs in ncRNAs-mediated cancer suppression and the molecular mechanisms.This review will help to provide beneficial clues related to the clinical use of CHMs in the cancer prevention and treatment and further promote new drug discovery against cancer.

Hybrid transcytosis nanopomegranates for sensitizing breast cancer radiotherapy in deep tumor tissue

As a standard cancer treatment method,radiotherapy(RT)has cured or alleviated over half cancer bearing patients worldwide more than 100 years.However,the therapeutic outcome is seriously hindered by the resistant tumor microenvironment(TME).Hypoxia is a critical factor of vicious TME that causes radiation resistance owing to the insufficiency of oxygen for DNA damage maintenance.Moreover,severe vascular dysfunction and pyknomorphic extracellular matrix(ECM)in deep tumor tissues substantially limit radiosensitizer penetration and oxygen diffusion from vessels into tightly packed tumor core.In this study,we develop a hybrid transcytosis nanopomegranate(HTP)with high transcytosis potential in response to TME condition.HTP is architected by self-assembly of small CuS and Au nanoparticles(NPs)at normal physiological condition.HTP can rapidly collapse to transcytosis NPs(CuS and Au NPs)in TME with cationized surface,which enables excellent transcytosis potential and effectively elevates the penetration of CuS and Au into deep tumor tissues.Following the second near-infrared(NIR(II))biowindow laser irradiation,CuS heats the tumor and enhances blood perfusion,eliciting tumor hypoxia alleviation and DNA damage aggravation.Moreover,Au NPs enriched in deep tumor tissues effectively sensitize radio-therapeutic response.Our study provides a new and potential nano-platform to ameliorate tumor hypoxia and sensitize deep tumor tissue radiotherapy.

Association between IDEAL-IQ MRI fat fraction quantification and pelvic bone marrow reserve function in concurrent chemoradiotherapy for cervical cancer

Objective:To analyze the association between iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification sequence(IDEAL-IQ)magnetic resonance imaging(MRI)of bone marrow fat fraction and bone marrow reserve function during concurrent chemoradiotherapy for cervical cancer.Methods:The study retrospectively analyzed twenty-six patients with stage IB1 to IVA cervical cancer treated between February 2020 and November 2020.All patients received concurrent chemoradiotherapy that included platinum alone or combined paclitaxel and platinum.Pelvic IDEAL-IQ MRI(plain and enhanced)was performed before and after treatment.Regions of interest,including the fifth lumbar vertebra,sacrum,ilium,ischium,and femoral neck,were manually delineated,and the bone marrow fat fraction was measured.Peripheral blood cell counts were recorded during treatment,and the relationship between the fat fraction values and changes in the blood cell counts was explored.Results:IDEAL-IQ MRI bone marrow fat fraction was associated with platelet nadir and platelet decline during treatment.The average pelvic bone marrow fat fraction before chemoradiotherapy was moderately negatively correlated with platelet count nadir during concurrent chemoradiotherapy(r=-0.450,P?0.021).The change in average pelvic bone marrow fat fraction through chemoradiotherapy was moderately positively correlated with the degree of thrombocytopenia(r=0.399,P=0.044).Conclusion:Bone marrow fat content quantified by IDEAL-IQ was associated with platelet count nadir and the degree of thrombocytopenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.

Added Value of Quantitative Apparent Diffusion Coefficients for Identifying Small Hepatocellular Carcinoma from Benign Nodule Categorized as LI-RADS 3 and 4 in Cirrhosis

Background and Aims:Correct identification of small hepa-tocellular carcinomas(HCCs)and benign nodules in cirrhosis remains challenging,quantitative apparent diffusion coeffi-cients(ADCs)have shown potential value in characterization of benign and malignant liver lesions.We aimed to explore the added value of ADCs in the identification of small(≤3 cm)HCCs and benign nodules categorized as Liver Imag-ing Reporting and Data System(LI-RADS)3(LR-3)and 4(LR-4)in cirrhosis.Methods:Ninety-seven cirrhosis patients with 109 small nodules(70 HCCs,39 benign nodules)of LR-3 and 4 LR-4 based on major and ancillary magnetic resonance imaging features were included.Multiparametric quantitative ADCs of the lesions,including the mean ADC(ADCmean),min-imum ADC(ADCmin),maximal ADC(ADCmax),ADC standard deviation(ADCstd),and mean ADC value ratio of lesion-to-liv-er parenchyma(ADCratio)were calculated.Regarding the joint diagnosis,a nomogram model was plotted using multivariate logistic regression analysis.The performance was assessed using the area under the receiver operating characteristic curve(AUC).Results:The ADCmean,ADCmin,ADCratio,and ADCstd were significantly associated with the identification of small HCC and benign nodules(p<0.001).For the joint diagnosis,the LI-RADS category(odds ratio[OR]=12.50),ADCmin(OR=0.14),and ADCratio(OR=0.12)were identified as independent factors for distinguishing HCCs from benign nodules.The joint nomogram model showed good calibration and discrimination,with a C-index of 0.947.Compared with the LI-RADS category alone,this nomogram model demon-strated a significant improvement in diagnostic performance,with AUC increasing from 0.820 to 0.967(p=0.001).Con-clusions:The addition of quantitative ADCs could improve the identification of small HCC and benign nodules catego-rized as LR-3 and 4 LR-4 in patients with cirrhosis.

EphA2:A promising therapeutic target in breast cancer

Ephrin type-A receptor 2(EphA2),a receptor tyrosine kinase,is overexpressed in human breast cancers often linked to poor patient prognosis.Accumulating evidence demonstrates that EphA2 plays important roles in several critical processes associated with malignant breast progression,such as proliferation,survival,migration,invasion,drug resistance,metastasis,and angiogenesis.As its inhibition through multiple approaches can inhibit the growth of breast cancer and restore drug sensitivity,EphA2 has become a promising therapeutic target for breast cancer treatment.Here,we summarize the expression,functions,mechanisms of action,and regulation of EphA2 in breast cancer.We also list the potential therapeutic strategies targeting EphA2.Furthermore,we discuss the future directions of studying EphA2 in breast cancer.

Dose Calculation Accuracy of Individualized Bulk Electron Density Assignment Approaches for Simulated MRI-only Planning of Thoracic Tumors

Objective This study aimed to investigate the dose calculation accuracy of individualized bulk electron density(IBED)assignment approaches for simulated magnetic resonance imaging(MRI)-only planning of thoracic tumors via the use of a 3 DVH system.Methods 8 patients with thoracic cancer were included in this study.Based on standard planning CT,single-arc dynamic conformal therapy(DCT)and double-arc volumetric modulated arc therapy(VMAT)plans with a6 MV photon beam were generated as a baseline plan(Plan-CT)for each patient.The simulated MRI-only planning(Plan-IBED)was implemented by copying the Plan-CT and forcing the electron density of each region of interest to its average value and recalculating the dose distribution.A 3 DVH system was used to visualize and compare the dosimetric differences between Plan-CT and Plan-IBED,and the criteria of the 3 D-Gamma pass rate were set to 1.0%/1.0 mm.Results The maximum percentage relative deviation(MPRD)of the dosimetric parameters D2,D95,D98,and Dmean of planning tumor volumes(PTVs)between Plan-CT and Plan-IBED was less than 1.3%.The MPRD of the average dose for organs at risk(OARs)was less than 1.5%.The MPRDs of the lung V5,V20,and V30 were 1.29%,3.26%,and 2.78%,respectively.Gamma analysis revealed an averaged pass rate of>95.0%for the body,as well as between 91.9%and 98.2%for OARs.Conclusion The proposed IBED assignment in simulated MRI-only treatment planning allows for dose calculation with comparable accuracy to the baseline plan and is appropriate for thoracic tumors.