Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic cha...Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.展开更多
Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dos...Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dose radio?therapy can improve the Qo L without affecting clinical efficacy is unknown.This study aimed to assess the survival rates and Qo L of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative(HPD).Methods:Forty?six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed.All patients were restaged according to the 7th edition of the American Joint Commit?tee on Cancer staging system.The radiotherapy plan was designed on the basis of pretreatment computed tomog?raphy.The OS,local recurrence?free survival(LRFS),distant metastasis?free survival(DMFS),and disease?free survival(DFS) rates were estimated using the Kaplan–Meier method.Qo L was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.Results:The 5?year OS,LRFS,DMFS,and DFS rates were 74.3%,72.6%,82.1%,and 61.2%,respectively.The corre?sponding 10?year rates were 38.4%,62.9%,78.5%,and 49.8%,respectively,and the 20?year rates were 27.7%,51.4%,78.5%,and 40.7%,respectively.None of the patients developed severe radiation?related complications,such as radiation?induced temporal lobe necrosis,hearing loss,trismus,and dysphagia.Conclusion:Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD,and this sensitivity was characterized by long?term survival without significant late treatment morbidities.展开更多
Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted the...Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted therapies,such as trastuzumab,have improved outcomes for HER2-positive breast cancer,challenges like therapy resistance persist,highlighting the need for novel treatments.Recent developments in antibody-drug conjugates(ADCs),particularly disitamab vedotin(RC48),show promising efficacy in targeting both HER2-positive and HER2-low expression tumors,warranting further investigation through real-world studies to assess its broader clinical applicability.Method:This retrospective,multicenter observational study evaluated the real-world efficacy and safety of RC48 in patients with HER2-positive or HER2-low breast cancer across three medical centers in China.Patient demographic characteristics,treatment patterns,sequential use of ADCs,and treatment-related adverse events were recorded and analyzed.Result:The median progression-free survival(mPFS)for the overall population(n 96)was=4.31 months,with HER2-positive patients demonstrating significantly longer mPFS(5.26 months)compared to HER2-low patients(3.45 months;p<0.044),while subgroup analyses revealed no significant differences in mPFS based on=estrogen receptor(ER),progesterone receptor(PR),or hormone receptor(HR)status.Safety data indicated that adverse events were consistent with prior reports,with no new safety concerns identified during the study period.Conclusion:This real-world study demonstrates the efficacy of RC48 in both HER2-positive and HER2-low breast cancer.Notably,combination therapy significantly improved outcomes in HER2-low patients.展开更多
Cancer is a leading cause of death in China with an estima- tion of nearly 2 million deaths every year （Chen and Fu, 2011b）. Matter of a public health importance in China and worldwide, the scientific community is s...Cancer is a leading cause of death in China with an estima- tion of nearly 2 million deaths every year （Chen and Fu, 2011b）. Matter of a public health importance in China and worldwide, the scientific community is still facing many obstacles to eradicate cancer： complexity of a mul- ti-factorial disease with organ-based specificities, high fail- ure rate of many anti-cancer drugs in clinical trials, lack of understanding of the cancer genesis factors.展开更多
Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored ro...Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.展开更多
BACKGROUND The survival rate of pancreatic cancer is low,and there is a lack of effective treatment.AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple c...BACKGROUND The survival rate of pancreatic cancer is low,and there is a lack of effective treatment.AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple chemotherapy regimens at different stages.METHODS This was a retrospective study conducted from 2005 to 2014,involving six cancer hospitals and eight general hospitals across seven geographical regions of China(East,South,North,Central,Southwest,Northwest,and Northeast).Stratified sampling was used based on the population distribution of each region.Efficacy assessments were conducted by Cox proportional hazards regression models.When assessing the effectiveness of various chemotherapy regimens,traditional drugs such as gemcitabine used as monotherapy served as the reference.RESULTS A total of 3256 patients were included.The median follow-up time was 407 days,and the median overall survival was 183 days.At diagnosis,56%of patients were already in stage IV.Chemotherapy was administered to 39.73%of patients.In the adjuvant therapy phase,gemcitabine+fluorouracil was superior to gemcitabine monotherapy[hazard ratio(HR)=0.35,95%confidence interval(CI):0.14-0.89].In fluorouracil-based regimens,other combination regimens did not show effectiveness relative to monotherapy.For first-line treatment in patients with advanced disease,tegafur alone(HR=0.20,95%CI:0.06-0.66),gemcitabine plus cisplatin(HR=0.16,95%CI:0.04-0.70),and tegafur,gemcitabine plus platinum-based agents(HR=0.32,95%CI:0.11-0.91)were associated with a lower risk of death compared to gemcitabine alone.In second-line treatment,there were no significant differences in efficacy among various drugs,but FOLFIRINOX(irinotecan+oxaliplatin+leucovorin+5-fluorouracil)had an outstanding point estimate(HR=0.10,95%CI:0.01-1.27).CONCLUSION In China,pancreatic cancer is often diagnosed at advanced stages,emphasizing the need for early diagnosis and treatment.Combined therapies in adjuvant and first-line settings may reduce the risk of death compared with monotherapy,and FOLFIRINOX might offer more significant benefits in second-line treatment.展开更多
Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for imp...Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement.Methods The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups.Kaplan–Meier plots were used to estimate the disease-specific survival(DSS)of the patients.The accuracy of the staging systems was investigated using the Harrell's concordance index(C-index).Results According to the 8th AJCC anatomic and prognostic stage groups,the 5-year DSS rates for patients with stages 0is/a,I,IIA,IIB,IIIA,IIIB,and IV disease were 100%,99%,86%,81%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–IIA)<0.001,p_(IIA–IIB)=0.5,p_(IIB–IIIA)<0.001,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).According to the modified model 1 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,88%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.002,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).Similarly,according to the modified model 2 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,86%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.008,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups.These results were confirmed by the bootstrap internal validation.Conclusion There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups.The improved models,which are more concise and convenient,have similar prediction accuracy.展开更多
Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-in...Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.展开更多
Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent...Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.展开更多
Objective:This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database,based on machine learning algorithms.Methods...Objective:This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database,based on machine learning algorithms.Methods:We analyzed the clinicopathological data of 3,926 gastrointestinal cancer patients from the Prevalence of Abdominal Complications After GastroEnterological surgery(PACAGE)database,covering 20 medical centers from December 2018 to December 2020.The predictive performance was evaluated using receiver operating characteristic(ROC)curves and Brier Score.Results:The patients were divided into gastric(2,271 cases)and colorectal cancer(1,655 cases)groups and further divided into training and external validation sets.The overall postoperative complication rates for gastric and colorectal cancer groups were 18.1%and 14.8%,respectively.The most common complication was the intraabdominal infection in both gastric and colorectal cancer groups.In the training set,the Random Forest(RF)model predicted the highest mean area under the curve(AUC)values for overall complications and different types of complications,in both the gastric cancer group and the colorectal cancer group,with similar results obtained in the external validation set.ROC curve analysis showed good predictive performance of the RF model for overall and infectious complications.An application-based clinical tool was developed for easy application in clinical practice.Conclusions:This model demonstrated good predictive performance for overall and infectious complications based on the multi-center database,supporting clinical decision-making and personalized treatment strategies.展开更多
Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cupropt...Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.展开更多
Background:A positive association between the ABO blood types and survival has been suggested in several malignancies.The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of ...Background:A positive association between the ABO blood types and survival has been suggested in several malignancies.The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer(NSCLC).Methods:We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1,2005 and December 31,2009.The relationship between the ABO blood types and survival was investigated.In addition,univariate and multivariate analyses were performed.Results:Group 1(patients with the blood type O or B) had significantly prolonged overall survival(OS) compared with group 2(patients with the blood type A or AB),with a median OS of 74.9 months versus 61.5 months[hazard ratio(HR) 0.83;95%confidence interval(CI) 0.72-0.96;P = 0.015].Additionally,group 1 had significantly longer disease-free survival(DFS;HR 0.86;95%CI 0.76-0.98;P = 0.022) and locoregional relapse-free survival(LRFS;HR 0.79;95%CI 0.64-0.98;P = 0.024) than group 2.The association was not significantly modified by other risk factors for NSCLC,including smoking status,pathologic tumor-node-metastasis stage,pT category,pN category,and chemotherapy.Conclusions:There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC.Patients with the blood type O or B had significantly prolonged OS,DFS,and LRFS compared with those with the blood type A or AB.展开更多
Objective： The automated breast ultrasound system（ABUS） is a potential method for breast cancer detection;however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic st...Objective： The automated breast ultrasound system（ABUS） is a potential method for breast cancer detection;however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic study to evaluate the clinical performance of the ABUS for breast cancer detection by comparing it to handheld ultrasound（HHUS） and mammography（MG）.Methods： Eligible participants underwent HHUS and ABUS testing; women aged 40–69 years additionally underwent MG. Images were interpreted using the Breast Imaging Reporting and Data System（BI-RADS）.Women in the BI-RADS categories 1–2 were considered negative. Women classified as BI-RADS 3 underwent magnetic resonance imaging to distinguish true-and false-negative results. Core aspiration or surgical biopsy was performed in women classified as BI-RADS 4–5, followed by a pathological diagnosis. Kappa values and agreement rates were calculated between ABUS, HHUS and MG.Results： A total of 1,973 women were included in the final analysis. Of these, 1,353（68.6%） and 620（31.4%）were classified as BI-RADS categories 1–3 and 4–5, respectively. In the older age group, the agreement rate and Kappa value between the ABUS and HHUS were 94.0% and 0.860（P〈0.001）, respectively; they were 89.2% and0.735（P〈0.001） between the ABUS and MG, respectively. Regarding consistency between imaging and pathology results, 78.6% of women classified as BI-RADS 4–5 based on the ABUS were diagnosed with precancerous lesions or cancer; which was 7.2% higher than that of women based on HHUS. For BI-RADS 1–2, the false-negative rates of the ABUS and HHUS were almost identical and were much lower than those of MG.Conclusions： We observed a good diagnostic reliability for the ABUS. Considering its performance for breast cancer detection in women with high-density breasts and its lower operator dependence, the ABUS is a promising option for breast cancer detection in China.展开更多
Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is co...Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy(LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. Methods: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. Results: A total of 63 patients underwent pancreaticoduodenectomy(PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss(200 vs. 400 m L, P < 0.001), lower proportion of intraoperative blood transfusion(16.0% vs. 39.5%, P = 0.047), longer operation time(390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay(11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively( P = 0.927). Conclusions: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.展开更多
Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,...Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.展开更多
Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to p...Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease.Methods:A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts.Multivariate logistic regression analysis was used to construct the nomogram.Model performance was evaluated by discrimination,calibration,and clinical usefulness.An independent multicenter cohort consisting of 250 patients was used for external validation.Results:A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9),CA125,CA50,and CA242.A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis:risk score of the four-marker signature,computed tomography-reported LN status,and clinical tumor stage.The prediction model exhibited good discrimination ability,with C-indexes of 0.806,0.742 and 0.763 for the development,internal validation,and external validation cohorts,respectively.The model also showed good calibration and clinical usefulness.A cut-off value(0.72)for the probability of LN metastasis was determined to separate low-risk and high-risk patients.Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status.Conclusions:This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.展开更多
Objective:Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer(mCRC)worldwide and was approved in China in 2010.However,there are limited real-world data o...Objective:Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer(mCRC)worldwide and was approved in China in 2010.However,there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC.This observational,phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.Methods:Between September 2013 and November 2016,patients with histologically confirmed mCRC were enrolled in a prospective,multicenter,observational,non-interventional phase IV trial at 26 centers across China.Eligible patients received different chemotherapeutic regimens combined with bevacizumab.The efficacy and safety data in the intention-to-treat study population were analyzed.Results:A total of 611 patients were included in the efficacy analysis.The median overall survival and median progression-free survival was 18.00 and 10.05 months,respectively.The objective response rate was 21.00%and disease control rate was 89.40%.In subgroup analyses,the survival differences were observed according to metastatic status,duration of treatment and elevation in blood pressure.A total of 613 patients were evaluable for safety assessments.And 569(92.82%)patients reported at least one adverse event(AE),and 151(24.63%)experienced grade 3 or higher AEs.The incidence of bevacizumab-associated AEs of special interest was reported in 31(5.06%)patients with hypertension(n=12),abscesses and fistulae(n=7),bleeding(n=6),proteinuria(n=3),gastrointestinal perforation(n=2)and venous thrombotic events(n=1).Conclusions:This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety.Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.展开更多
Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrenc...Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.展开更多
Objective:We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus(hrHPV)-positive women in primary healthcare settings in China.Methods:This study was undertaken in 11 ...Objective:We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus(hrHPV)-positive women in primary healthcare settings in China.Methods:This study was undertaken in 11 rural and 9 urban sites.Women aged 35-64 years old were enrolled.HrHPV-positive women were randomly allocated to liquid-based cytology(LBC),visual inspection with acetic acid and Lugol’s iodine(VIA/VILI)(rural only)triage,or directly referred to colposcopy(direct COLP).At 24 months,hrHPV testing,LBC and VIA/VILI were conducted for combined screening.Results:In rural sites,1,949 hrHPV-positive women were analyzed.A total of 852,218 and 480 women were randomly assigned to direct COLP,LBC and VIA/VILI.At baseline,colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%.LBC(n=3 and n=7)or VIA/VILI(n=8 and n=26)could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia(CIN)2 or worse and CIN3+compared with direct COLP(n=14 and n=23).For the 24-month cumulative detection rate of CIN2+,VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP.When stratified by age,baseline LBC triage+performed best(P<0.001),peaking among women aged 35-44 years(Ptrend=0.002).In urban sites,1,728 women were hrHPV genotyping test positive.A total of 408,571 and 568women were randomly assigned to direct COLP for HPV16/18+,direct COLP for other hrHPV subtypes+,and LBC triage for other hrHPV subtypes+.LBC(n=12 and n=31)significantly decreased the number of colposcopies needed to detect one CIN2+and CIN3+compared with direct COLP(n=14 and n=44).HPV16/18+increased the 24-month cumulative detection rate of CIN2+(17.89%,P<0.001).Conclusions:LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+women and LBC triage for other hrHPV subtype+women in urban settings might be feasible strategies.展开更多
Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, w...Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81172568)
文摘Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.
基金supported by the National Key Technologies Research and Development Program of China(No.85-914-02)the National Natural Science Foundation of China(No.30770641,31170805)
文摘Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dose radio?therapy can improve the Qo L without affecting clinical efficacy is unknown.This study aimed to assess the survival rates and Qo L of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative(HPD).Methods:Forty?six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed.All patients were restaged according to the 7th edition of the American Joint Commit?tee on Cancer staging system.The radiotherapy plan was designed on the basis of pretreatment computed tomog?raphy.The OS,local recurrence?free survival(LRFS),distant metastasis?free survival(DMFS),and disease?free survival(DFS) rates were estimated using the Kaplan–Meier method.Qo L was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.Results:The 5?year OS,LRFS,DMFS,and DFS rates were 74.3%,72.6%,82.1%,and 61.2%,respectively.The corre?sponding 10?year rates were 38.4%,62.9%,78.5%,and 49.8%,respectively,and the 20?year rates were 27.7%,51.4%,78.5%,and 40.7%,respectively.None of the patients developed severe radiation?related complications,such as radiation?induced temporal lobe necrosis,hearing loss,trismus,and dysphagia.Conclusion:Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD,and this sensitivity was characterized by long?term survival without significant late treatment morbidities.
基金funded by the medical and health category of the Science and Technology Project of Shantou(No.230509116495542,Wu Haoming)National Natural Science Foundation of China(NSFC)Cultivation Project of the Cancer Hospital of Shantou University Medical College(No.2024GP002,Wu Haoming)National Natural Science Foundation of China(82203130,Ye Feng).
文摘Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted therapies,such as trastuzumab,have improved outcomes for HER2-positive breast cancer,challenges like therapy resistance persist,highlighting the need for novel treatments.Recent developments in antibody-drug conjugates(ADCs),particularly disitamab vedotin(RC48),show promising efficacy in targeting both HER2-positive and HER2-low expression tumors,warranting further investigation through real-world studies to assess its broader clinical applicability.Method:This retrospective,multicenter observational study evaluated the real-world efficacy and safety of RC48 in patients with HER2-positive or HER2-low breast cancer across three medical centers in China.Patient demographic characteristics,treatment patterns,sequential use of ADCs,and treatment-related adverse events were recorded and analyzed.Result:The median progression-free survival(mPFS)for the overall population(n 96)was=4.31 months,with HER2-positive patients demonstrating significantly longer mPFS(5.26 months)compared to HER2-low patients(3.45 months;p<0.044),while subgroup analyses revealed no significant differences in mPFS based on=estrogen receptor(ER),progesterone receptor(PR),or hormone receptor(HR)status.Safety data indicated that adverse events were consistent with prior reports,with no new safety concerns identified during the study period.Conclusion:This real-world study demonstrates the efficacy of RC48 in both HER2-positive and HER2-low breast cancer.Notably,combination therapy significantly improved outcomes in HER2-low patients.
文摘Cancer is a leading cause of death in China with an estima- tion of nearly 2 million deaths every year （Chen and Fu, 2011b）. Matter of a public health importance in China and worldwide, the scientific community is still facing many obstacles to eradicate cancer： complexity of a mul- ti-factorial disease with organ-based specificities, high fail- ure rate of many anti-cancer drugs in clinical trials, lack of understanding of the cancer genesis factors.
基金supported by the National Natural Science Foundation of China(grant no.81602426).
文摘Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.
文摘BACKGROUND The survival rate of pancreatic cancer is low,and there is a lack of effective treatment.AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple chemotherapy regimens at different stages.METHODS This was a retrospective study conducted from 2005 to 2014,involving six cancer hospitals and eight general hospitals across seven geographical regions of China(East,South,North,Central,Southwest,Northwest,and Northeast).Stratified sampling was used based on the population distribution of each region.Efficacy assessments were conducted by Cox proportional hazards regression models.When assessing the effectiveness of various chemotherapy regimens,traditional drugs such as gemcitabine used as monotherapy served as the reference.RESULTS A total of 3256 patients were included.The median follow-up time was 407 days,and the median overall survival was 183 days.At diagnosis,56%of patients were already in stage IV.Chemotherapy was administered to 39.73%of patients.In the adjuvant therapy phase,gemcitabine+fluorouracil was superior to gemcitabine monotherapy[hazard ratio(HR)=0.35,95%confidence interval(CI):0.14-0.89].In fluorouracil-based regimens,other combination regimens did not show effectiveness relative to monotherapy.For first-line treatment in patients with advanced disease,tegafur alone(HR=0.20,95%CI:0.06-0.66),gemcitabine plus cisplatin(HR=0.16,95%CI:0.04-0.70),and tegafur,gemcitabine plus platinum-based agents(HR=0.32,95%CI:0.11-0.91)were associated with a lower risk of death compared to gemcitabine alone.In second-line treatment,there were no significant differences in efficacy among various drugs,but FOLFIRINOX(irinotecan+oxaliplatin+leucovorin+5-fluorouracil)had an outstanding point estimate(HR=0.10,95%CI:0.01-1.27).CONCLUSION In China,pancreatic cancer is often diagnosed at advanced stages,emphasizing the need for early diagnosis and treatment.Combined therapies in adjuvant and first-line settings may reduce the risk of death compared with monotherapy,and FOLFIRINOX might offer more significant benefits in second-line treatment.
基金supported by the Guangdong Province Nature Foundation of China Project (No. 2022A1515012200 to Li Z)Shenzhen Science and Technology Program (No. RCYX20221008093032008 to Li Z)Shenzhen People's Hospital Clinician Scientist Training Program (No. SYWGSJCYJ202405 to Li Z).
文摘Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement.Methods The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups.Kaplan–Meier plots were used to estimate the disease-specific survival(DSS)of the patients.The accuracy of the staging systems was investigated using the Harrell's concordance index(C-index).Results According to the 8th AJCC anatomic and prognostic stage groups,the 5-year DSS rates for patients with stages 0is/a,I,IIA,IIB,IIIA,IIIB,and IV disease were 100%,99%,86%,81%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–IIA)<0.001,p_(IIA–IIB)=0.5,p_(IIB–IIIA)<0.001,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).According to the modified model 1 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,88%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.002,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).Similarly,according to the modified model 2 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,86%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.008,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups.These results were confirmed by the bootstrap internal validation.Conclusion There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups.The improved models,which are more concise and convenient,have similar prediction accuracy.
基金Noncommunicable Chronic Diseases-National Science and Technology Major Project,Grant/Award Numbers:2024ZD0521400,2024ZD0521404Affiliated Hospital of Qinghai University。
文摘Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.
基金supported by the National Natural Science Foundation of China(No.82574683)the National Natural Science Foundation of Science and Technology Department of Sichuan Province(Nos.2023NSFSC1928 and 2023NSFSC1992)+2 种基金Project of State Administration of Traditional Chinese Medicine of China(No.ZYYCXTD-D-202209)Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2022C001)Fundamental Research Funds for the Central Universities(No.YJ201880).
文摘Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.
基金supported by the Natural Science Foundation of Fujian Province(No.2022J01755)。
文摘Objective:This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database,based on machine learning algorithms.Methods:We analyzed the clinicopathological data of 3,926 gastrointestinal cancer patients from the Prevalence of Abdominal Complications After GastroEnterological surgery(PACAGE)database,covering 20 medical centers from December 2018 to December 2020.The predictive performance was evaluated using receiver operating characteristic(ROC)curves and Brier Score.Results:The patients were divided into gastric(2,271 cases)and colorectal cancer(1,655 cases)groups and further divided into training and external validation sets.The overall postoperative complication rates for gastric and colorectal cancer groups were 18.1%and 14.8%,respectively.The most common complication was the intraabdominal infection in both gastric and colorectal cancer groups.In the training set,the Random Forest(RF)model predicted the highest mean area under the curve(AUC)values for overall complications and different types of complications,in both the gastric cancer group and the colorectal cancer group,with similar results obtained in the external validation set.ROC curve analysis showed good predictive performance of the RF model for overall and infectious complications.An application-based clinical tool was developed for easy application in clinical practice.Conclusions:This model demonstrated good predictive performance for overall and infectious complications based on the multi-center database,supporting clinical decision-making and personalized treatment strategies.
基金supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)+2 种基金Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
文摘Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
文摘Background:A positive association between the ABO blood types and survival has been suggested in several malignancies.The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer(NSCLC).Methods:We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1,2005 and December 31,2009.The relationship between the ABO blood types and survival was investigated.In addition,univariate and multivariate analyses were performed.Results:Group 1(patients with the blood type O or B) had significantly prolonged overall survival(OS) compared with group 2(patients with the blood type A or AB),with a median OS of 74.9 months versus 61.5 months[hazard ratio(HR) 0.83;95%confidence interval(CI) 0.72-0.96;P = 0.015].Additionally,group 1 had significantly longer disease-free survival(DFS;HR 0.86;95%CI 0.76-0.98;P = 0.022) and locoregional relapse-free survival(LRFS;HR 0.79;95%CI 0.64-0.98;P = 0.024) than group 2.The association was not significantly modified by other risk factors for NSCLC,including smoking status,pathologic tumor-node-metastasis stage,pT category,pN category,and chemotherapy.Conclusions:There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC.Patients with the blood type O or B had significantly prolonged OS,DFS,and LRFS compared with those with the blood type A or AB.
文摘Objective： The automated breast ultrasound system（ABUS） is a potential method for breast cancer detection;however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic study to evaluate the clinical performance of the ABUS for breast cancer detection by comparing it to handheld ultrasound（HHUS） and mammography（MG）.Methods： Eligible participants underwent HHUS and ABUS testing; women aged 40–69 years additionally underwent MG. Images were interpreted using the Breast Imaging Reporting and Data System（BI-RADS）.Women in the BI-RADS categories 1–2 were considered negative. Women classified as BI-RADS 3 underwent magnetic resonance imaging to distinguish true-and false-negative results. Core aspiration or surgical biopsy was performed in women classified as BI-RADS 4–5, followed by a pathological diagnosis. Kappa values and agreement rates were calculated between ABUS, HHUS and MG.Results： A total of 1,973 women were included in the final analysis. Of these, 1,353（68.6%） and 620（31.4%）were classified as BI-RADS categories 1–3 and 4–5, respectively. In the older age group, the agreement rate and Kappa value between the ABUS and HHUS were 94.0% and 0.860（P〈0.001）, respectively; they were 89.2% and0.735（P〈0.001） between the ABUS and MG, respectively. Regarding consistency between imaging and pathology results, 78.6% of women classified as BI-RADS 4–5 based on the ABUS were diagnosed with precancerous lesions or cancer; which was 7.2% higher than that of women based on HHUS. For BI-RADS 1–2, the false-negative rates of the ABUS and HHUS were almost identical and were much lower than those of MG.Conclusions： We observed a good diagnostic reliability for the ABUS. Considering its performance for breast cancer detection in women with high-density breasts and its lower operator dependence, the ABUS is a promising option for breast cancer detection in China.
基金supported by grants from the National Natural Science Foundation of China (82072693, 81902417 and 82172884)the Scientific Innovation Project of Shanghai Education Commit-tee (2019-01-07-00-07-E00057)+2 种基金Clinical and Scientific Innovation Project of Shanghai Hospital Development Center (SHDC12018109)Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1006A)National Key Research and Development Program of China (2020YFA0803202)。
文摘Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy(LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. Methods: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. Results: A total of 63 patients underwent pancreaticoduodenectomy(PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss(200 vs. 400 m L, P < 0.001), lower proportion of intraoperative blood transfusion(16.0% vs. 39.5%, P = 0.047), longer operation time(390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay(11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively( P = 0.927). Conclusions: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.
文摘Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.
基金supported by grants from the National Natural Science Foundation of China(81772555,81802352 and 81902428)the National Science Foundation for Distinguished Young Scholars of China(81625016)+4 种基金the Shanghai Sailing Program(19YF1409400 and 20YF1409000)the Shanghai Rising-Star Program(20QA1402100)the Shanghai Anticancer Association Young Eagle Program(SACA-CY19A06)the Clinical and Scientific Innovation Project of Shanghai Hospital Development Center(SHDC12018109 and SHDC12019109)the Scientific Innovation Project of Shanghai Education Committee(2019-01-07-00-07-E00057)。
文摘Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease.Methods:A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts.Multivariate logistic regression analysis was used to construct the nomogram.Model performance was evaluated by discrimination,calibration,and clinical usefulness.An independent multicenter cohort consisting of 250 patients was used for external validation.Results:A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9),CA125,CA50,and CA242.A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis:risk score of the four-marker signature,computed tomography-reported LN status,and clinical tumor stage.The prediction model exhibited good discrimination ability,with C-indexes of 0.806,0.742 and 0.763 for the development,internal validation,and external validation cohorts,respectively.The model also showed good calibration and clinical usefulness.A cut-off value(0.72)for the probability of LN metastasis was determined to separate low-risk and high-risk patients.Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status.Conclusions:This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.
文摘Objective:Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer(mCRC)worldwide and was approved in China in 2010.However,there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC.This observational,phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.Methods:Between September 2013 and November 2016,patients with histologically confirmed mCRC were enrolled in a prospective,multicenter,observational,non-interventional phase IV trial at 26 centers across China.Eligible patients received different chemotherapeutic regimens combined with bevacizumab.The efficacy and safety data in the intention-to-treat study population were analyzed.Results:A total of 611 patients were included in the efficacy analysis.The median overall survival and median progression-free survival was 18.00 and 10.05 months,respectively.The objective response rate was 21.00%and disease control rate was 89.40%.In subgroup analyses,the survival differences were observed according to metastatic status,duration of treatment and elevation in blood pressure.A total of 613 patients were evaluable for safety assessments.And 569(92.82%)patients reported at least one adverse event(AE),and 151(24.63%)experienced grade 3 or higher AEs.The incidence of bevacizumab-associated AEs of special interest was reported in 31(5.06%)patients with hypertension(n=12),abscesses and fistulae(n=7),bleeding(n=6),proteinuria(n=3),gastrointestinal perforation(n=2)and venous thrombotic events(n=1).Conclusions:This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety.Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.
文摘Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.
基金National Health Commission(formerly Health and Family Planning Commission)of China(No.201502004)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-004)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2019PT320010 and No.2018PT32025)。
文摘Objective:We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus(hrHPV)-positive women in primary healthcare settings in China.Methods:This study was undertaken in 11 rural and 9 urban sites.Women aged 35-64 years old were enrolled.HrHPV-positive women were randomly allocated to liquid-based cytology(LBC),visual inspection with acetic acid and Lugol’s iodine(VIA/VILI)(rural only)triage,or directly referred to colposcopy(direct COLP).At 24 months,hrHPV testing,LBC and VIA/VILI were conducted for combined screening.Results:In rural sites,1,949 hrHPV-positive women were analyzed.A total of 852,218 and 480 women were randomly assigned to direct COLP,LBC and VIA/VILI.At baseline,colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%.LBC(n=3 and n=7)or VIA/VILI(n=8 and n=26)could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia(CIN)2 or worse and CIN3+compared with direct COLP(n=14 and n=23).For the 24-month cumulative detection rate of CIN2+,VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP.When stratified by age,baseline LBC triage+performed best(P<0.001),peaking among women aged 35-44 years(Ptrend=0.002).In urban sites,1,728 women were hrHPV genotyping test positive.A total of 408,571 and 568women were randomly assigned to direct COLP for HPV16/18+,direct COLP for other hrHPV subtypes+,and LBC triage for other hrHPV subtypes+.LBC(n=12 and n=31)significantly decreased the number of colposcopies needed to detect one CIN2+and CIN3+compared with direct COLP(n=14 and n=44).HPV16/18+increased the 24-month cumulative detection rate of CIN2+(17.89%,P<0.001).Conclusions:LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+women and LBC triage for other hrHPV subtype+women in urban settings might be feasible strategies.
文摘Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal
