Objective： To evaluate the feasibility of DNA image cytometry （DNA-ICM） as a primary screening method for esophageal squamous cell cancer （ESCC）. Methods： A total of 5,382 local residents aged 40-69 years from t...Objective： To evaluate the feasibility of DNA image cytometry （DNA-ICM） as a primary screening method for esophageal squamous cell cancer （ESCC）. Methods： A total of 5,382 local residents aged 40-69 years from three high-risk areas in China （Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province） from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol＇s iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity （SE）, specificity （SP）, negative predictive values （NPV） and positive predictive values （PPV） as well as their 95% confidence intervals （95% CI） for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic （ROC） curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results： DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions （X2= 18.016, P〈0.001）. The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia （LGIN）, high grade intraepithelial neoplasia （HGIN）, and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test （cutoff point 5,803） combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance （ASCUS）] were separately 72.1% （95% CI： 70.3%-73.9%）, 43.3% （95% CI. 41.3%-45.3%）, 22.8% （95% CI： 21.1%-24.5%） and 87.0% （95% CI： 85.7%-88.3%） for LGIN, 85.7% （95% CI： 84.3%-87.1%）, 41.3% （95% CI： 39.3%-43.3%）, 4.6% （95% CI： 3.8%-5.4%） and 98.9% （95% CI： 98.5%-99.3%） for HGIN, and 96.0% （95% CI： 95.2%-96.8%）, 40.8% （95% CI： 38.8%-42.8%）, 1.7% （95% CI： 1.2%-2.2%） and 99.9% （95% CI： 99.8%-100.0%） for ESCC. Conclusions： It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.展开更多
BACKGROUND Pancreatic cancer has an extremely poor prognosis.Although surgery is the firstline treatment for pancreatic cancer,its role is ultimately limited because patients often present too late for resection.Thus,...BACKGROUND Pancreatic cancer has an extremely poor prognosis.Although surgery is the firstline treatment for pancreatic cancer,its role is ultimately limited because patients often present too late for resection.Thus,multidisciplinary treatment approaches are needed.In particular,chemotherapy,targeted therapy,and immunotherapy can be ineffective for locally advanced pancreatic cancer(LAPC)because of its resistance to these modalities,but cryoablation has shown significant promise for treating this entity and prolonging survival.AIM To investigate the safety and efficacy of cryoablation for LAPC.METHODS Clinical and laboratory data,including surgical procedure,postoperative complications,immunobiochemical markers(e.g.,carbohydrate antigen 19-9),and followup visits,of 24 LAPC patients treated with cryoablation at the department of hepatobiliary and pancreatic surgery of our hospital from January 2023 to December 2024 were retrospectively analyzed.RESULTS Surgery was smooth in all patients,with no perioperative deaths.Postoperative pancreatic fistulas occurred in 18 patients(75.0%),including biochemical leak in 14 cases and grade B(fistula)in 4 cases.Three patients(12.5%)had delayed gastric emptying.The carbohydrate antigen 19-9 level remained low on postoperative day 30(P<0.05).Immune markers(natural killer cells and tumor necrosis factor-alpha)significantly increased on days 7 and 30(P<0.01 or P<0.05),whereas cluster of differentiation CD4+T cells levels on day 30 significantly differed from baseline.Day 30 pain scores were significantly lower than preoperative ones(P<0.01).Tumor volume was reduced on postoperative computed tomography.Survival was prolonged.The overall survival time of LAPC patients treated with cryoablation was 16.8 months.CONCLUSION Cryoablation can directly inactivate LAPC and boost immunity,thus delaying tumor progression,alleviating pain,improving quality of life,and prolonging survivals.Therefore,it is a safe and effective treatment option for LAPC.展开更多
BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with...BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.展开更多
Objective：Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer.The purpose of this study was to identify the common and characteristic...Objective：Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer.The purpose of this study was to identify the common and characteristic preoperative ultrasonography features that are associated with the pathologic extranodal extension of metastatic papillary thyroid carcinoma.Methods：We retrospectively assessed and compared clinicopathologic and ultrasound features between 60 papillary thyroid cancer patients with extranodal extension and 120 control patients with papillary thyroid cancer without extranodal extension.Results：With respect to the pathological N stage and clinicopathologic features,N1b stage papillary thyroid carcinomas were more frequently found in patients who were extranodal extension-positive,in comparison with those who were extranodal extension-negative（78.3%vs.63.3%,P=0.043）.Extranodal extension was detected most frequently in level VI cervical lymph nodes（48.7%）.In our univariate analysis of patients with papillary thyroid carcinoma,cervical lymph nodes with extranodal extension showed higher incidences of node matting,microcalcification,cystic area,aspect ratio＆lt;2,and larger diameter than those without extranodal extension（all P〈0.05）.Our multivariate analysis demonstrated that node matting and cystic area were independent risk factors for the presence of extranodal extension[odds ratio（OR）：4.751,95%confidence interval（CI）：1.212~18.626,P=0.025;OR：2.707,95%CI：1.127~6.502,P=0.026].Conclusions：Common ultrasound features may indicate the presence of extranodal extension in patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.展开更多
As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligentl...As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligently sift through various contributions,ranging from comprehensive reviews to original articles and other scholarly works.Through meticulous examination,we discern the most notable papers,delving into each with careful scrutiny to distill their merits and shortcomings.Undoubtedly,this undertaking demands considerable time and effort.Yet,it stands as an indispensable pursuit,affording us a profound comprehension of the latest breakthroughs in CRC research.Moreover,these meticulously curated selections furnish readers with invaluable resources,serving as enduring references for the nuanced exploration of this dynamic field.展开更多
Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclon...Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.展开更多
Background Metastatic lung cancer(LC)is a threat to human health.We previously proposed a fat age-inflammation(FAIN)index which showed prognostic value in patients with certain cancers.However,whether a similar associ...Background Metastatic lung cancer(LC)is a threat to human health.We previously proposed a fat age-inflammation(FAIN)index which showed prognostic value in patients with certain cancers.However,whether a similar association exists in patients with metastatic LC remains unknown.Methods We performed a cohort study including 1360 patients with metastatic LC from January 2013 to April 2019.The FAIN index was defined as:(triceps skinfold thickness+albumin)/[age+5×(neutrophil count/lymphocyte count)]×100%.Sex-specific cutoffs of the FAIN were determined using an optimal stratification approach.The associations of the FAIN index with the nutrition related factors,short-term outcomes and overall survival(OS)of patients were comprehensively assessed.Results The study enrolled 865 males and 495 females with a median age of 59.9 years.The continuous FAIN was significantly associated with the OS in both genders(both P<0.05).The optimal stratification-defined FAIN cutoffs were 82 for women and 60 for men.A total of 623 patients(45.8%)were categorized as having a low FAIN.A low FAIN was associated with poorer nutrition-related factors and impaired short-term outcomes including the thirty-day mortality,length of hospital stay,intensive care unit stay and cost(all P<0.05).Multivariate Cox regression analysis revealed that a lower FAIN was also associated with an increased death hazard(HR=1.428,95%CI=1.209-1.686).Conclusion This study assessed the FAIN index,which might act as a feasible tool to monitor nutrition-related factors and help develop management strategies to optimize the clinical outcomes of patients with metastatic LC.展开更多
The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from ...The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.展开更多
Objective：To identify and isolate CD133 positive cancer stem-like cells （CD133^＋ cells） from the highly invasive human hepatocellular carcinoma cell Iine（MHCC97H）, and examine their potential for clonogenicity a...Objective：To identify and isolate CD133 positive cancer stem-like cells （CD133^＋ cells） from the highly invasive human hepatocellular carcinoma cell Iine（MHCC97H）, and examine their potential for clonogenicity and tumorigenicity. Methods： CD133^＋ and CD133^- cells were isolated from MHCC97H cell line by magnetic bead cell sorting（MACS）, and the potentials of CD133^＋ cells for colony formation and tumorigenicity were evaluated by soft agar cloning and tumor formation following nude mice inoculation. Results：CD133^＋ cells represent a minority（0.5-2.0%） of the tumor cell population with a greater colony-forming efficiency and greater tumor production ability. The colony-forming efficiency of CD133^＋ cells in soft agar was significantly higher than CD133^- cells（36.8 ± 1.4 vs 12.9 ± 0.8, P 〈 0.05）. After 6 weeks, 3/5 mice inoculated with 1 × 10^3 CD133^＋ cells, 4/5 with 1 × 10^4 CD133^＋ cells and 5/5 with 1× 10^5 CD133^＋ cells developed detectable tumors at the injection site, while only one tumor was found in mice treated with same numbers of CD133 cells. Conclusion： CD133 may be a hallmark of liver cancer stem cells （CSC） in human hepatocellular carcinoma（HCC）, because the CD133^＋ cells identified and isolated with anti-CD133 labeled magnetic beads from MHCC97H cell line exhibit high potentials for clonogenicity and tumorigenicity. These CD 133^＋ cells might contribute to hepatocarcinogenesis, as well as the growth and recurrence of human HCC, and therefore may be a useful target for anti-cancer therapy.展开更多
<strong>Introduction: </strong>Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts an...<strong>Introduction: </strong>Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. <strong>Patients and</strong> <strong>Methods: </strong>There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. <strong>Results: </strong>Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. <strong>Conclusion: </strong>Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.展开更多
Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies ...Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).展开更多
BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer.Many molecular genetic changes are associated with its occurrence.Raman spectroscopy has become a new method for the e...BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer.Many molecular genetic changes are associated with its occurrence.Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level.AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia.METHODS Different grades of esophageal lesions were collected,and a total of 360 groups of Raman spectrum data were collected.A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma.In addition,a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics.RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm^(-1)(DNA,symmetric PO,and stretching vibration),1132 cm^(-1)(cytochrome c),1171 cm^(-1)(acetoacetate),1216 cm^(-1)(amide III),and 1315 cm^(-1)(glycerol).A comparison among the training results of different models revealed that the 1Dtransformer network performed best.A 93.30%accuracy value,a 96.65%specificity value,a 93.30%sensitivity value,and a 93.17%F1 score were achieved.CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia.The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.展开更多
In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology.They explored an innovative approach to enhancing gemcitabine(GEM)delivery an...In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology.They explored an innovative approach to enhancing gemcitabine(GEM)delivery and efficacy using human bone marrow mesenchymal stem cells(HU-BMSCs)-derived exosomes.The manufacture of GEM-loaded HU-BMSCs-derived exosomes(Exo-GEM)has been optimized.The Tang et al’s study demonstrated that Exo-GEM exhibits enhanced cytotoxicity and apoptosis-inducing effects compared to free GEM,highlighting the potential of exosome-based drug delivery systems as a more effective and targeted approach to chemotherapy in pancreatic cancer.Additional in vivo studies are required to confirm the safety and effectiveness of Exo-GEM before it can be considered for clinical use.展开更多
BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as le...BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.展开更多
In this article,we evaluate the findings of the study by Qian et al,which explores the efficacy of combining hyperthermia with opioid therapy for enhanced cancer pain management in patients with middle and late-stage ...In this article,we evaluate the findings of the study by Qian et al,which explores the efficacy of combining hyperthermia with opioid therapy for enhanced cancer pain management in patients with middle and late-stage gastrointestinal tumors.The study undertakes a retrospective analysis comparing traditional opioid therapy to an integrated approach of hyperthermia and opioids across 70 patients,highlighting significant benefits in pain control,reduction of opioid dosage,and minimization of adverse reactions.In our article,we not only discuss these fin-dings but also emphasize the broader implications for clinical practice,parti-cularly in enhancing patient outcomes through innovative pain management strategies.We advocate for further research to establish more robust data su-pporting this approach and to explore the mechanistic insights that enable these benefits.This discussion reflects on the potential paradigm shift in managing debilitating cancer-related pain,urging a reevaluation of current practices to incorporate these findings effectively.展开更多
Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall surviva...Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPa)signaling pathway may provide a novel strategy for GI cancers treatment.This study summarizes current knowledge of the structure and function of CD47 and SIRPa,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.展开更多
BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regim...BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase Ⅲ clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.展开更多
Immune checkpoint inhibitor(ICI)has limited efficacy in the treatment of immune“cold”tumors.Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1(PD-L1)expression,the ORR is only 5%–8%...Immune checkpoint inhibitor(ICI)has limited efficacy in the treatment of immune“cold”tumors.Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1(PD-L1)expression,the ORR is only 5%–8%compared with 30%–40%of“hot”tumors.This article reviews the synergistic mechanism,clinical efficacy and optimization strategy of oncolytic virus(OVs)combined with ICIs in the treatment of refractory malignant tumors.Systematic analysis of mechanistic interactions across tumor types and clinical trial data demonstrates that OVs transform the immunosuppressive microenvironment by inducing immunogenic cell death and activating innate immunity.Concurrently,ICIs enhance adaptive immunity by reversing T-cell exhaustion and expanding T-cell diversity.Clinical trials in melanoma,head and neck cancer and breast cancer showed superior efficacy.The Objective Response Rate(ORR)of combination therapy was 39%–62%,while the ORR of ICI monotherapy was 18%.Treatment heterogeneity is mainly attributed to virus-related factors,including targeting specificity and replication efficiency,tumor characteristics,such as antigen presenting ability and mutation load,and host immune status,including preexisting antiviral antibodies and microbiome composition.This combined approach represents a paradigm shift in cancer immunotherapy,which effectively transforms immune“cold”tumors into“hot”tumors through the continuous activation of innate and adaptive immune responses.In the future,it is expected to improve the therapeutic effect of treatment-resistant malignant tumors through the integration of immune regulatory molecules,accurate biomarkers to guide the treatment scheme and triple combination strategy by a new generation of engineering viruses.展开更多
Background Human behaviors and tumors go hand in hand.The wave of globalization has brought about a global homogenization of human behaviors,which further triggers a potential global human behavior-related cancer burd...Background Human behaviors and tumors go hand in hand.The wave of globalization has brought about a global homogenization of human behaviors,which further triggers a potential global human behavior-related cancer burden(HBRCB)convergence.Methods This study systematically evaluated the global,regional,and national metrics of HBRCBs over the last 30 years using data from the Global Burden of Diseases(GBD)2019 results and the WHO Global Health Observatory(GHO)data repository.Results The results showed the global remission and convergence of HBRCB in the last three decades and the foreseeable future(2020–2044).Overall,HBRCBs are decreasing with the global emphasis on positive dietary habits,safe sex,substance addiction withdrawal,and active physical exercise habits.Globally,from 1990 to 2019,with the development of social development index(SDI)level from 0.511 to 0.651,the HBRCBs had been decreasing from 1507.908 to 1145.344 in age-standardized disability-adjusted life years(ASDALY)and from 61.467 to 49.449 in(age-standardized death rates)ASDR per 100,000 population with changes of−24.04%and−19.55%,respectively.Meanwhile,the variance in HBRCBs among countries and territories generally showed a decreasing or flat trend.The variance of HBRCBs among 204 countries and territories in 2019–2044 decreased from 1495.210 to 449.202 in males and from 214.640 to 78.848 in females for ASDR due to all behavior risks,and from 911,211.676 to 317,233.590 in males and from 146,171.660 to 62,926.660 in females for ASDALY.The global HBRCBs was becoming more uniform due to the globalization of human behaviors.Conclusions This study revealed the significance of addressing HBRCBs as a uniform and continuous issue in future global health promotion.It also demonstrated the potential existence of a chain effect in global health,where globalization leads to human behavior homogenization,which in turn results in HBRCB convergence.Properly measuring the commonalities and individualities among different regions and finding a balance when designing and evaluating HBRCB-related global policies in the global convergence trend of HBRCBs will be major concerns in the future.展开更多
BACKGROUND Ubiquitin-specific protease 15(USP15)is an important member of the ubiquitinspecific protease family,the largest deubiquitinase subfamily,whose expression is dysregulated in many types of cancer.However,the...BACKGROUND Ubiquitin-specific protease 15(USP15)is an important member of the ubiquitinspecific protease family,the largest deubiquitinase subfamily,whose expression is dysregulated in many types of cancer.However,the biological function and the underlying mechanisms of USP15 in gastric cancer(GC)progression have not been elucidated.AIM To explore the biological role and underlying mechanisms of USP15 in GC progression.METHODS Bioinformatics databases and western blot analysis were utilized to determine the expression of USP15 in GC.Immunohistochemistry was performed to evaluate the correlation between USP15 expression and clinicopathological characteristics of patients with GC.A loss-and gain-of-function experiment was used to investigate the biological effects of USP15 on GC carcinogenesis.RNA sequencing,immunofluorescence,and western blotting were performed to explore the potential mechanism by which USP15 exerts its oncogenic functions.RESULTS USP15 was up-regulated in GC tissue and cell lines.The expression level of USP15 was positively correlated with clinical characteristics(tumor size,depth of invasion,lymph node involvement,tumor-node-metastasis stage,perineural invasion,and vascular invasion),and was related to poor prognosis.USP15 knockdown significantly inhibited cell proliferation,invasion and epithelialmesenchymal transition(EMT)of GC in vitro,while overexpression of USP15 promoted these processes.Knockdown of USP15 inhibited tumor growth in vivo.Mechanistically,RNA sequencing analysis showed that USP15 regulated the Wnt signaling pathway in GC.Western blotting confirmed that USP15 silencing led to significant down-regulation ofβ-catenin and Wnt/β-catenin downstream genes(c-myc and cyclin D1),while overexpression of USP15 yielded an opposite result and USP15 mutation had no change.Immunofluorescence indicated that USP15 promoted nuclear translocation ofβ-catenin,suggesting activation of the Wnt/β-catenin signaling pathway,which may be the critical mechanism promoting GC progression.Finally,rescue experiments showed that the effect of USP15 on gastric cancer progression was dependent on Wnt/β-catenin pathway.CONCLUSION USP15 promotes cell proliferation,invasion and EMT progression of GC via regulating the Wnt/β-catenin pathway,which suggests that USP15 is a novel potential therapeutic target for GC.展开更多
基金granted by the National Natural Science Foundation of China (No.81241091)
文摘Objective： To evaluate the feasibility of DNA image cytometry （DNA-ICM） as a primary screening method for esophageal squamous cell cancer （ESCC）. Methods： A total of 5,382 local residents aged 40-69 years from three high-risk areas in China （Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province） from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol＇s iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity （SE）, specificity （SP）, negative predictive values （NPV） and positive predictive values （PPV） as well as their 95% confidence intervals （95% CI） for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic （ROC） curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results： DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions （X2= 18.016, P〈0.001）. The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia （LGIN）, high grade intraepithelial neoplasia （HGIN）, and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test （cutoff point 5,803） combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance （ASCUS）] were separately 72.1% （95% CI： 70.3%-73.9%）, 43.3% （95% CI. 41.3%-45.3%）, 22.8% （95% CI： 21.1%-24.5%） and 87.0% （95% CI： 85.7%-88.3%） for LGIN, 85.7% （95% CI： 84.3%-87.1%）, 41.3% （95% CI： 39.3%-43.3%）, 4.6% （95% CI： 3.8%-5.4%） and 98.9% （95% CI： 98.5%-99.3%） for HGIN, and 96.0% （95% CI： 95.2%-96.8%）, 40.8% （95% CI： 38.8%-42.8%）, 1.7% （95% CI： 1.2%-2.2%） and 99.9% （95% CI： 99.8%-100.0%） for ESCC. Conclusions： It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.
文摘BACKGROUND Pancreatic cancer has an extremely poor prognosis.Although surgery is the firstline treatment for pancreatic cancer,its role is ultimately limited because patients often present too late for resection.Thus,multidisciplinary treatment approaches are needed.In particular,chemotherapy,targeted therapy,and immunotherapy can be ineffective for locally advanced pancreatic cancer(LAPC)because of its resistance to these modalities,but cryoablation has shown significant promise for treating this entity and prolonging survival.AIM To investigate the safety and efficacy of cryoablation for LAPC.METHODS Clinical and laboratory data,including surgical procedure,postoperative complications,immunobiochemical markers(e.g.,carbohydrate antigen 19-9),and followup visits,of 24 LAPC patients treated with cryoablation at the department of hepatobiliary and pancreatic surgery of our hospital from January 2023 to December 2024 were retrospectively analyzed.RESULTS Surgery was smooth in all patients,with no perioperative deaths.Postoperative pancreatic fistulas occurred in 18 patients(75.0%),including biochemical leak in 14 cases and grade B(fistula)in 4 cases.Three patients(12.5%)had delayed gastric emptying.The carbohydrate antigen 19-9 level remained low on postoperative day 30(P<0.05).Immune markers(natural killer cells and tumor necrosis factor-alpha)significantly increased on days 7 and 30(P<0.01 or P<0.05),whereas cluster of differentiation CD4+T cells levels on day 30 significantly differed from baseline.Day 30 pain scores were significantly lower than preoperative ones(P<0.01).Tumor volume was reduced on postoperative computed tomography.Survival was prolonged.The overall survival time of LAPC patients treated with cryoablation was 16.8 months.CONCLUSION Cryoablation can directly inactivate LAPC and boost immunity,thus delaying tumor progression,alleviating pain,improving quality of life,and prolonging survivals.Therefore,it is a safe and effective treatment option for LAPC.
基金Supported by the Science and Technology Program of Lu’an,No.2022 Lakj042.
文摘BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.
文摘Objective：Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer.The purpose of this study was to identify the common and characteristic preoperative ultrasonography features that are associated with the pathologic extranodal extension of metastatic papillary thyroid carcinoma.Methods：We retrospectively assessed and compared clinicopathologic and ultrasound features between 60 papillary thyroid cancer patients with extranodal extension and 120 control patients with papillary thyroid cancer without extranodal extension.Results：With respect to the pathological N stage and clinicopathologic features,N1b stage papillary thyroid carcinomas were more frequently found in patients who were extranodal extension-positive,in comparison with those who were extranodal extension-negative（78.3%vs.63.3%,P=0.043）.Extranodal extension was detected most frequently in level VI cervical lymph nodes（48.7%）.In our univariate analysis of patients with papillary thyroid carcinoma,cervical lymph nodes with extranodal extension showed higher incidences of node matting,microcalcification,cystic area,aspect ratio＆lt;2,and larger diameter than those without extranodal extension（all P〈0.05）.Our multivariate analysis demonstrated that node matting and cystic area were independent risk factors for the presence of extranodal extension[odds ratio（OR）：4.751,95%confidence interval（CI）：1.212~18.626,P=0.025;OR：2.707,95%CI：1.127~6.502,P=0.026].Conclusions：Common ultrasound features may indicate the presence of extranodal extension in patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.
基金Supported by The Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713The Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06。
文摘As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligently sift through various contributions,ranging from comprehensive reviews to original articles and other scholarly works.Through meticulous examination,we discern the most notable papers,delving into each with careful scrutiny to distill their merits and shortcomings.Undoubtedly,this undertaking demands considerable time and effort.Yet,it stands as an indispensable pursuit,affording us a profound comprehension of the latest breakthroughs in CRC research.Moreover,these meticulously curated selections furnish readers with invaluable resources,serving as enduring references for the nuanced exploration of this dynamic field.
基金funded by Sinocelltech Ltd, Beijing Chinapartly supported by China National Major Project for New Drug Innovation (No. 2012ZX09303012 and No. 2017ZX09304015)
文摘Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.
基金the Talent Innovation Capacity Development Program of Army Medical Center of PLA(2019CXJSC003,to Hong Xia Xu)National Key Research and Development Program(2017YFC1309200).
文摘Background Metastatic lung cancer(LC)is a threat to human health.We previously proposed a fat age-inflammation(FAIN)index which showed prognostic value in patients with certain cancers.However,whether a similar association exists in patients with metastatic LC remains unknown.Methods We performed a cohort study including 1360 patients with metastatic LC from January 2013 to April 2019.The FAIN index was defined as:(triceps skinfold thickness+albumin)/[age+5×(neutrophil count/lymphocyte count)]×100%.Sex-specific cutoffs of the FAIN were determined using an optimal stratification approach.The associations of the FAIN index with the nutrition related factors,short-term outcomes and overall survival(OS)of patients were comprehensively assessed.Results The study enrolled 865 males and 495 females with a median age of 59.9 years.The continuous FAIN was significantly associated with the OS in both genders(both P<0.05).The optimal stratification-defined FAIN cutoffs were 82 for women and 60 for men.A total of 623 patients(45.8%)were categorized as having a low FAIN.A low FAIN was associated with poorer nutrition-related factors and impaired short-term outcomes including the thirty-day mortality,length of hospital stay,intensive care unit stay and cost(all P<0.05).Multivariate Cox regression analysis revealed that a lower FAIN was also associated with an increased death hazard(HR=1.428,95%CI=1.209-1.686).Conclusion This study assessed the FAIN index,which might act as a feasible tool to monitor nutrition-related factors and help develop management strategies to optimize the clinical outcomes of patients with metastatic LC.
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.
文摘Objective：To identify and isolate CD133 positive cancer stem-like cells （CD133^＋ cells） from the highly invasive human hepatocellular carcinoma cell Iine（MHCC97H）, and examine their potential for clonogenicity and tumorigenicity. Methods： CD133^＋ and CD133^- cells were isolated from MHCC97H cell line by magnetic bead cell sorting（MACS）, and the potentials of CD133^＋ cells for colony formation and tumorigenicity were evaluated by soft agar cloning and tumor formation following nude mice inoculation. Results：CD133^＋ cells represent a minority（0.5-2.0%） of the tumor cell population with a greater colony-forming efficiency and greater tumor production ability. The colony-forming efficiency of CD133^＋ cells in soft agar was significantly higher than CD133^- cells（36.8 ± 1.4 vs 12.9 ± 0.8, P 〈 0.05）. After 6 weeks, 3/5 mice inoculated with 1 × 10^3 CD133^＋ cells, 4/5 with 1 × 10^4 CD133^＋ cells and 5/5 with 1× 10^5 CD133^＋ cells developed detectable tumors at the injection site, while only one tumor was found in mice treated with same numbers of CD133 cells. Conclusion： CD133 may be a hallmark of liver cancer stem cells （CSC） in human hepatocellular carcinoma（HCC）, because the CD133^＋ cells identified and isolated with anti-CD133 labeled magnetic beads from MHCC97H cell line exhibit high potentials for clonogenicity and tumorigenicity. These CD 133^＋ cells might contribute to hepatocarcinogenesis, as well as the growth and recurrence of human HCC, and therefore may be a useful target for anti-cancer therapy.
文摘<strong>Introduction: </strong>Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. <strong>Patients and</strong> <strong>Methods: </strong>There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. <strong>Results: </strong>Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. <strong>Conclusion: </strong>Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.
基金funded by Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)National Natural Science Foundation of China(Grant No.82103677)National Science and Technology Major Projects of China(Grant No.2019ZX09732-001)。
文摘Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).
基金Supported by Beijing Hospitals Authority Youth Programme,No.QML20200505.
文摘BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer.Many molecular genetic changes are associated with its occurrence.Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level.AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia.METHODS Different grades of esophageal lesions were collected,and a total of 360 groups of Raman spectrum data were collected.A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma.In addition,a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics.RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm^(-1)(DNA,symmetric PO,and stretching vibration),1132 cm^(-1)(cytochrome c),1171 cm^(-1)(acetoacetate),1216 cm^(-1)(amide III),and 1315 cm^(-1)(glycerol).A comparison among the training results of different models revealed that the 1Dtransformer network performed best.A 93.30%accuracy value,a 96.65%specificity value,a 93.30%sensitivity value,and a 93.17%F1 score were achieved.CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia.The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.
基金Supported by the grants of China Medical University Hospital,No.DMR-112-173 and No.DMR-113-089the grant from Tungs’Taichung Metro Harbor Hospital,No.TTMHH-R1120013.
文摘In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal Oncology.They explored an innovative approach to enhancing gemcitabine(GEM)delivery and efficacy using human bone marrow mesenchymal stem cells(HU-BMSCs)-derived exosomes.The manufacture of GEM-loaded HU-BMSCs-derived exosomes(Exo-GEM)has been optimized.The Tang et al’s study demonstrated that Exo-GEM exhibits enhanced cytotoxicity and apoptosis-inducing effects compared to free GEM,highlighting the potential of exosome-based drug delivery systems as a more effective and targeted approach to chemotherapy in pancreatic cancer.Additional in vivo studies are required to confirm the safety and effectiveness of Exo-GEM before it can be considered for clinical use.
基金Supported by the Capital’s Funds for Health Improvement and Research,No.SF202222175.
文摘BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.
基金Supported by the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘In this article,we evaluate the findings of the study by Qian et al,which explores the efficacy of combining hyperthermia with opioid therapy for enhanced cancer pain management in patients with middle and late-stage gastrointestinal tumors.The study undertakes a retrospective analysis comparing traditional opioid therapy to an integrated approach of hyperthermia and opioids across 70 patients,highlighting significant benefits in pain control,reduction of opioid dosage,and minimization of adverse reactions.In our article,we not only discuss these fin-dings but also emphasize the broader implications for clinical practice,parti-cularly in enhancing patient outcomes through innovative pain management strategies.We advocate for further research to establish more robust data su-pporting this approach and to explore the mechanistic insights that enable these benefits.This discussion reflects on the potential paradigm shift in managing debilitating cancer-related pain,urging a reevaluation of current practices to incorporate these findings effectively.
基金supported by the Fundamental Research Funds for the Central Universities,China(Grant Nos.:2023CDJXY-009 and 2023CDJYGRH-YB07)the National Natural Science Foundation of China(Grant No.:82172888)the Natural Science Foundation Project of Chongqing Science and Technology Commission(Grant No.:cstc2020jcyj-msxmX0154).
文摘Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPa)signaling pathway may provide a novel strategy for GI cancers treatment.This study summarizes current knowledge of the structure and function of CD47 and SIRPa,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.
基金Supported by CAMS Innovation Fund for Medical Sciences CIFMS,No.2023-I2M-3-012.
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase Ⅲ clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.
基金supported in part by grants from the National Natural Science Foundation ofChina(Nos.82260462,82460606,32360046)Yunnan Fundamental Research Kunming Medical University Joint Projects(Nos.202201AY0700001-144,202301AY070001-115)+2 种基金Yunnan Fundamental Research Projects(No.202201AT070269)Yunnan health training project of high level talents(Nos.D-2024007,H-2024023)Graduate Innovation Fund of Kunming Medical University(No.2025S100).
文摘Immune checkpoint inhibitor(ICI)has limited efficacy in the treatment of immune“cold”tumors.Due to insufficient T cell infiltration and heterogeneous programmed death ligand 1(PD-L1)expression,the ORR is only 5%–8%compared with 30%–40%of“hot”tumors.This article reviews the synergistic mechanism,clinical efficacy and optimization strategy of oncolytic virus(OVs)combined with ICIs in the treatment of refractory malignant tumors.Systematic analysis of mechanistic interactions across tumor types and clinical trial data demonstrates that OVs transform the immunosuppressive microenvironment by inducing immunogenic cell death and activating innate immunity.Concurrently,ICIs enhance adaptive immunity by reversing T-cell exhaustion and expanding T-cell diversity.Clinical trials in melanoma,head and neck cancer and breast cancer showed superior efficacy.The Objective Response Rate(ORR)of combination therapy was 39%–62%,while the ORR of ICI monotherapy was 18%.Treatment heterogeneity is mainly attributed to virus-related factors,including targeting specificity and replication efficiency,tumor characteristics,such as antigen presenting ability and mutation load,and host immune status,including preexisting antiviral antibodies and microbiome composition.This combined approach represents a paradigm shift in cancer immunotherapy,which effectively transforms immune“cold”tumors into“hot”tumors through the continuous activation of innate and adaptive immune responses.In the future,it is expected to improve the therapeutic effect of treatment-resistant malignant tumors through the integration of immune regulatory molecules,accurate biomarkers to guide the treatment scheme and triple combination strategy by a new generation of engineering viruses.
基金supported by the Development Center for Medical Science and Technology National Health Commission of the People's Republic of China(WA2021RW27).
文摘Background Human behaviors and tumors go hand in hand.The wave of globalization has brought about a global homogenization of human behaviors,which further triggers a potential global human behavior-related cancer burden(HBRCB)convergence.Methods This study systematically evaluated the global,regional,and national metrics of HBRCBs over the last 30 years using data from the Global Burden of Diseases(GBD)2019 results and the WHO Global Health Observatory(GHO)data repository.Results The results showed the global remission and convergence of HBRCB in the last three decades and the foreseeable future(2020–2044).Overall,HBRCBs are decreasing with the global emphasis on positive dietary habits,safe sex,substance addiction withdrawal,and active physical exercise habits.Globally,from 1990 to 2019,with the development of social development index(SDI)level from 0.511 to 0.651,the HBRCBs had been decreasing from 1507.908 to 1145.344 in age-standardized disability-adjusted life years(ASDALY)and from 61.467 to 49.449 in(age-standardized death rates)ASDR per 100,000 population with changes of−24.04%and−19.55%,respectively.Meanwhile,the variance in HBRCBs among countries and territories generally showed a decreasing or flat trend.The variance of HBRCBs among 204 countries and territories in 2019–2044 decreased from 1495.210 to 449.202 in males and from 214.640 to 78.848 in females for ASDR due to all behavior risks,and from 911,211.676 to 317,233.590 in males and from 146,171.660 to 62,926.660 in females for ASDALY.The global HBRCBs was becoming more uniform due to the globalization of human behaviors.Conclusions This study revealed the significance of addressing HBRCBs as a uniform and continuous issue in future global health promotion.It also demonstrated the potential existence of a chain effect in global health,where globalization leads to human behavior homogenization,which in turn results in HBRCB convergence.Properly measuring the commonalities and individualities among different regions and finding a balance when designing and evaluating HBRCB-related global policies in the global convergence trend of HBRCBs will be major concerns in the future.
基金Supported by National Natural Science Foundation of China,No.81760432Science and Technology Department of Jiangxi Province,No.20202BBGL73036and Jiangxi Provincial Outstanding Young Talents Projects,No.20204BCJ23016.
文摘BACKGROUND Ubiquitin-specific protease 15(USP15)is an important member of the ubiquitinspecific protease family,the largest deubiquitinase subfamily,whose expression is dysregulated in many types of cancer.However,the biological function and the underlying mechanisms of USP15 in gastric cancer(GC)progression have not been elucidated.AIM To explore the biological role and underlying mechanisms of USP15 in GC progression.METHODS Bioinformatics databases and western blot analysis were utilized to determine the expression of USP15 in GC.Immunohistochemistry was performed to evaluate the correlation between USP15 expression and clinicopathological characteristics of patients with GC.A loss-and gain-of-function experiment was used to investigate the biological effects of USP15 on GC carcinogenesis.RNA sequencing,immunofluorescence,and western blotting were performed to explore the potential mechanism by which USP15 exerts its oncogenic functions.RESULTS USP15 was up-regulated in GC tissue and cell lines.The expression level of USP15 was positively correlated with clinical characteristics(tumor size,depth of invasion,lymph node involvement,tumor-node-metastasis stage,perineural invasion,and vascular invasion),and was related to poor prognosis.USP15 knockdown significantly inhibited cell proliferation,invasion and epithelialmesenchymal transition(EMT)of GC in vitro,while overexpression of USP15 promoted these processes.Knockdown of USP15 inhibited tumor growth in vivo.Mechanistically,RNA sequencing analysis showed that USP15 regulated the Wnt signaling pathway in GC.Western blotting confirmed that USP15 silencing led to significant down-regulation ofβ-catenin and Wnt/β-catenin downstream genes(c-myc and cyclin D1),while overexpression of USP15 yielded an opposite result and USP15 mutation had no change.Immunofluorescence indicated that USP15 promoted nuclear translocation ofβ-catenin,suggesting activation of the Wnt/β-catenin signaling pathway,which may be the critical mechanism promoting GC progression.Finally,rescue experiments showed that the effect of USP15 on gastric cancer progression was dependent on Wnt/β-catenin pathway.CONCLUSION USP15 promotes cell proliferation,invasion and EMT progression of GC via regulating the Wnt/β-catenin pathway,which suggests that USP15 is a novel potential therapeutic target for GC.
