Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in mo...Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in most patients,BCG failure occurs in 30%–50%of patients and a progression to muscle-invasive disease is found in 10%–15%.Therefore,predicting high-risk patients who might not benefit from BCG treatment is critical.The purpose of this study was to identify,whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.Methods:Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into“responders”and“non-responders”groups.Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.Results:Mutations in TP53,FGFR3,PIK3CA,KRAS,CTNNB1,ALK and DDR2 genes were detected.TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort(31.6%and 26.3%,respectively),followed by PIK3CA(15.8%).In the BCG-responsive patient group,90%of samples were found to have mutated genes,with almost 50%of them showing mutations in tyrosine kinase receptors and CTNNB1 genes.On the other hand,in the BCG-unresponsive group,we found mutations in 44.4%of samples,mainly in TP53 gene.Conclusions:Our findings suggest that a Next-Generation Sequencing(NGS)multigene panel is useful in predicting BCG response in patients with NMIBC.展开更多
The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breas...The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.展开更多
Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-co...Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-conjugated epirubicin liposomes by incorporating a synthesized folate-lipid derivative; and to assess the effects on cellular drug uptake, co-localization of drug with nuclei and efficacy in treatment of invasive breast cancer cells. The studies were performed on invasive human breast cancer cells. The folate-PEG2ooo-DSPE conjugate was synthesized, and the constructed folate-conjugated epirubicin liposomes were approximately 1 O0 nm in size. The in vitro studies demonstrated that the folate-conjugated epirubicin liposomes had the strongest cellular drug uptake and co-localization with nuclei of the invasive breast cancer cells. Besides, the liposomes displayed the most significant efficacy in killing the invasive cancer cells, in preventing their invasive potential, and in penetrating ability into breast cancer spheroid as well. In conclusion, the constructed folate-conjugated epirubicin liposomes were able to enhance the efficacy in treatment of invasive breast cancer by improving the cellular drug uptake and increasing the co-localization with nuclei, hence offering a new strategy for potentially eradicating the invasive breast cancer cells.展开更多
Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management...Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.展开更多
Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinica...Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.展开更多
AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer. METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radioth...AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer. METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as "front-positive" and in 41% as "front-negative". The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the "front-positive" tumors. CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.展开更多
Objective:Neoadjuvant chemotherapy followed by radical cystectomy is considered the standard of care for patients with muscle invasive bladder cancer.In the last decade,interest in neoadjuvant chemotherapy has slowly ...Objective:Neoadjuvant chemotherapy followed by radical cystectomy is considered the standard of care for patients with muscle invasive bladder cancer.In the last decade,interest in neoadjuvant chemotherapy has slowly shifted from methotrexate,vinblastine,doxorubicin and cisplatin regime to gemcitabine and cisplatin regime.There are many publications on gemcitabine and cisplatin regime in literature which cover different aspects of treatment.This review aims to summarise the findings published so far on gemcitabine and cisplatin regime and present it in a concise manner.Methods:A systematic literature review was conducted searching the PubMeddatabase in December 2016 using the medical subject heading(MeSH)with the terms gemcitabine,cisplatin,chemotherapy,muscle invasive bladder cancer,and neoadjuvant.All relevant studies were included and results were analysed.Results:A total of 13 studies were included which published between 2007 and 2015.These 13 studies comprised of 754 subjects suffering from muscle invasive bladder cancer.The proportion of male patients ranged from 60%to 86.4%and the median age ranged from 54.2 to 77.3 years in various studies.Complete pathological response(pT0)was seen in 30.0%of patients and pathological downstaging(<pT2)was seen in 48.67%of patients.Conclusion:As per latest guidelines,neoadjuvant chemotherapy is recommended for patients with muscle invasive bladder cancer.There is substantial pathological downstaging with low toxicity in patients of muscle invasive bladder cancer who receive neoadjuvant gemcitabine and cisplatin regime.展开更多
Objective:THigh-risk non-invasive bladder cancer(NMIBC)has a high rate of recurrence and disease progression.At present,there are still insufficient effective prevention and treatment methods,especially for patients w...Objective:THigh-risk non-invasive bladder cancer(NMIBC)has a high rate of recurrence and disease progression.At present,there are still insufficient effective prevention and treatment methods,especially for patients who have failed BCG treatment.This article reviews the research progress of the molecular mechanism of BCG unresponsive NMIBC,and summarizes the current status and prospects of emerging therapeutic strategies represented by immunotherapy,providing a theoretical basis for the immunotherapy of BCG non-reactive NMIBC.Methods:We searched the PubMed and CNKI journal full-text database search system for keywords"non-muscle invasive bladder cancer,BCG unresponsive,disease recurrence,disease progression,and immunotherapy"with 126 English and 538 Chinese articles.The literature,as well as the relevant clinical research in ClinicalTrials.gov,were integrated together to obtain the results.Results:Immunotherapy was performed in various types of tumors,and the use of immunotherapeutic drugs with different oncotargets administered alone,sequentially or in combination for the treatment of BCG-unresponsive NMIBC have achieved favorable effects,and more Clinical research is still ongoing.Conclusion:Immunotherapy is currently the most promising treatment for cancer,and it is indispensable for patients with NMIBC,both biologically and clinically.We look forward to more laboratory and clinical research in immunotherapy in the future.展开更多
The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characte...The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.展开更多
Objectives: Previous reviews reported the outcome of each scientific modality in the management of T1 high-grade bladder cancer. The objective of this review is to assess and evaluate the available scientific modaliti...Objectives: Previous reviews reported the outcome of each scientific modality in the management of T1 high-grade bladder cancer. The objective of this review is to assess and evaluate the available scientific modalities used during the last two decades and determine whether they were able to improve the clinical outcome. Literature Search Methodology: A systematic literature review was conducted from 2000-2020 using PubMed, Medline, Embase, and other database sites looking at randomized controlled trials (RCTs), clinical trials, research, review articles, and original articles addressing the different scientific modalities used to diagnose and manage patients with non-muscle invasive Bladder cancer (NMIBC)during the last 2 decades. More than 573 studies were retrieved following the preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and PICOS criteria (Population, Intervention, Comparators, Outcomes, and Study design). Only 85 articles were selected for review including 19 prospective trials, 44 RCTs, original articles, research articles, one review article, and clinical trials—Retrospective studies were excluded to limit bias as much as possible in the analysis. Results: Randomized controlled trials (RCTs) have become the gold standard for evaluating the efficacy of new treatments. They are considered the highest standard of evidence-based medicine and are the method of choice. Overall, we selected 85 studies for review, among them 63 prospective trials and RCTs, with a total of 21,895 patients, published between 2000 and 2020. Previously conducted studies have shown that identifying rare histological types with poor prognoses can help improve outcomes, mainly the plasmacytoid type. Many articles addressed the role of biomarkers in the early identification of patients with NMIBC for recurrence and progression—P-cadherin expression and others were used to predict recurrence and/or progression with promising results. Despite the need for modifications, risk stratification is an important tool that should be used to improve the outcome of patients with NMIBC. Some found that fluorescence diagnostic cystoscopy (FDC) and Photodynamic diagnosis (PDD) improved recurrence-free survival but not progression and outcome. All authors agree that intravesical BCG is the most effective therapy that changes the course of high-grade T1 mainly progression. Re-TURBT has become one of the recommendations of international societies, but its potential effect on survival improvement is debatable. Most of the articles showed the advantages of early cystectomy in NMIBC but all agree that the selection criteria must be clearly defined. Conclusions: This review analyzed the outcomes provided by the scientific advances in the field of management of NMIBC patients in the last two decades. Patients with T1 bladder cancer have variable outcomes because of tumor heterogeneity and clinical staging. Despite the great development in the field of diagnosis, risk stratification, and management, further large studies are mostly needed to better elucidate this subset of patients and avoid over and under-treatment.展开更多
BACKGROUND Transcatheter arterial chemoembolization(TACE)is a key treatment approach for advanced invasive liver cancer(infiltrative hepatocellular carcinoma).However,its therapeutic response can be difficult to evalu...BACKGROUND Transcatheter arterial chemoembolization(TACE)is a key treatment approach for advanced invasive liver cancer(infiltrative hepatocellular carcinoma).However,its therapeutic response can be difficult to evaluate accurately using conventional two-dimensional imaging criteria due to the tumor’s diffuse and multifocal growth pattern.Volumetric imaging,especially enhanced tumor volume(ETV),offers a more comprehensive assessment.Nonetheless,bias field inhomogeneity in magnetic resonance imaging(MRI)poses challenges,potentially skewing volumetric measurements and undermining prognostic evaluation.AIM To investigate whether MRI bias field correction enhances the accuracy of volumetric assessment of infiltrative hepatocellular carcinoma treated with TACE,and to analyze how this improved measurement impacts prognostic prediction.METHODS We retrospectively collected data from 105 patients with invasive liver cancer who underwent TACE treatment at the Affiliated Hospital of Xuzhou Medical University from January 2020 to January 2024.The improved N4 bias field correction algorithm was applied to process MRI images,and the ETV before and after treatment was calculated.The ETV measurements before and after correction were compared,and their relationship with patient prognosis was analyzed.A Cox proportional hazards model was used to evaluate prognostic factors,with Martingale residual analysis determining the optimal cutoff value,followed by survival analysis.RESULTS Bias field correction significantly affected ETV measurements,with the corrected baseline ETV mean(505.235 cm^(3))being significantly lower than before correction(825.632 cm^(3),P<0.001).Cox analysis showed that the hazard ratio(HR)for corrected baseline ETV(HR=1.165,95%CI:1.069-1.268)was higher than before correction(HR=1.063,95%CI:1.031-1.095).Using 412 cm^(3) as the cutoff,the group with baseline ETV<415 cm^(3) had a longer median survival time compared to the≥415 cm^(3) group(18.523 months vs 8.926 months,P<0.001).The group with an ETV reduction rate≥41%had better prognosis than the<41%group(17.862 months vs 9.235 months,P=0.006).Multivariate analysis confirmed that ETV reduction rate(HR=0.412,P<0.001),Child-Pugh classification(HR=0.298,P<0.001),and Barcelona Clinic Liver Cancer stage(HR=0.578,P=0.045)were independent prognostic factors.CONCLUSION Volume imaging based on MRI bias field correction can improve the accuracy of evaluating the efficacy of TACE treatment for invasive liver cancer.The corrected ETV and its reduction rate can serve as independent indicators for predicting patient prognosis,providing important reference for developing individualized treatment strategies.展开更多
Objective: To explore the diagnostic value of serum tumor markers CEA, AFP, CA199, CA125, CA153, CYFRA21, CA724, and NSE in invasive breast cancer. Methods: A total of 314 patients with invasive breast cancer from Bao...Objective: To explore the diagnostic value of serum tumor markers CEA, AFP, CA199, CA125, CA153, CYFRA21, CA724, and NSE in invasive breast cancer. Methods: A total of 314 patients with invasive breast cancer from Baoding First Central Hospital between January 2021 and December 2022, and 31 patients with benign breast diseases (including mastitis, breast fibroadenoma, breast adenosis, adenoma of the breast, benign phyllodes tumor of the breast, and intraductal papilloma) were randomly selected as the control group. The levels of CEA, AFP, CA199, CA125, CA153, CYFRA21, CA724, and NSE were measured using electrochemiluminescence. Results: The serum concentrations of CEA, CA153, and CYFRA21 showed significant statistical differences between the invasive breast cancer group and the benign breast disease group (P < 0.01). ROC curve analysis revealed that CA153 had the highest sensitivity for diagnosing invasive breast cancer, while CEA had the highest specificity, at 84.4% and 77.4%, respectively. When multiple tumor markers were used for the diagnosis of invasive breast cancer, the combination of CEA and CA153 showed the highest specificity at 90.3%, while the combination of CEA and CYFRA21 had the highest sensitivity at 88.2%. The combined detection of CEA, CYFRA21, and CA153 had the largest area under the curve (AUC) on the ROC curve, at 0.802, indicating that the combination of these three markers provided the best diagnostic performance for invasive breast cancer. Conclusion: CEA, CA153, and CYFRA21 can be used for the diagnosis of invasive breast cancer, and the combined detection of these three markers offers the best diagnostic efficacy for invasive breast cancer.展开更多
Invasive-squamous-cell-cancer(ISCC)of the anal canal is an uncommon disease.Human papillomavirus(HPV)is the etiological agent of most of types of ISCC.The incidence of ISCC has been increasing in HIV-infected individu...Invasive-squamous-cell-cancer(ISCC)of the anal canal is an uncommon disease.Human papillomavirus(HPV)is the etiological agent of most of types of ISCC.The incidence of ISCC has been increasing in HIV-infected individuals,even after the introduction of highly active antiretroviral therapy.The aim of this study was to analyze biopsy specimens from patients diagnosed with ISCC at a tertiary hospital from 1983 to 2012 in order to detect HPV-DNA.Methods:Formaldehyde-fixed,paraffin-embedded specimens from patients with ISCC underwent HPV-DNA genotyping using multiplex PCR assay.Results:A total of 31 cases were collected;10 were HIV-infected(9 men,1 woman)and 21 non-HIV-infected(11 men,10 women).HPV infection was detected in 87.5%(7/8)of the HIV-infected patients(DNA from 2 biopsies was degraded)and 76.2%(16/21)of non-HIV-infected individuals.Multiple-type infections were only found in 28.6%(2/7)of the HIV-infected patients(no multiple-type infections in non-HIV-infected individuals).The most prevalent type was HPV-16:50%(4/8)in the HIV-infected group(57%[4/7]of the HPV-positive samples)and 66.7%(14/21)in the non-HIV-infected group(87.5%(14/16)of the HPV-positive samples).Remarkably,37.5%(3/8)of the HIV-infected group had high-risk HPV types not included in the vaccines(HPV-33,51,52,and 66)compared with 4.8%in the non-HIV-infected group(1/21,HPV-52).All cases of anal ISCC in HIV-infected patients were recorded in the highly active antiretroviral therapy era.Conclusion:HIV-infected patients presented anal ISCC with a higher proportion of high-risk HPV types not covered by the conventional vaccines than non-HIV-infected individuals.展开更多
Objective To assess the feasibility and clinical efficacy of minimally invasive esophagectomy for esophageal cancer. Methods From July 2007 to December 2009,eighty-one patients with esophageal cancer received combined...Objective To assess the feasibility and clinical efficacy of minimally invasive esophagectomy for esophageal cancer. Methods From July 2007 to December 2009,eighty-one patients with esophageal cancer received combined thoracoscopic and laparoscopic esophagectomy with anastomosis in the neck. All clinical data were retrospectively reviewed. Results The median operative展开更多
BACKGROUND Endoscopic ultrasound(EUS)stands as an accurate imaging modality for esophageal cancer staging,however utilization of EUS in early-stage cancer management remains controversial.Identification of non-applica...BACKGROUND Endoscopic ultrasound(EUS)stands as an accurate imaging modality for esophageal cancer staging,however utilization of EUS in early-stage cancer management remains controversial.Identification of non-applicability of endoscopic interventions with deep muscular invasion with EUS in pre-intervention evaluation of early-stage esophageal cancer is compared to endoscopic and histologic indicators.AIM To display the role of EUS in pre-intervention early esophageal cancer staging and how the index endoscopic features of invasive esophageal malignancy compare for prediction of depth of invasion and cancer management.METHODS This was a retrospective study of patients who underwent pre-resection EUS after a diagnosis of esophageal cancer at a tertiary medical center from 2012 to 2022.Patient clinical data,initial esophagogastroduodenoscopy/biopsy,EUS,and final resection pathology reports were abstracted,and statistical analysis was conducted to assess the role of EUS in management decisions.RESULTS Forty nine patients were identified for this study.EUS T stage was concordant with histological T stage in 75.5%of patients.In determining submucosal involvement(T1a vs T1b),EUS had a specificity of 85.0%,sensitivity of 53.9%,and accuracy of 72.7%.Endoscopic features of tumor size>2 cm and the presence of esophageal ulceration were significantly associated with deep invasion of cancer on histology.EUS affected management from endoscopic mucosal resection/submucosal dissection to esophagectomy in 23.5%of patients without esophageal ulceration and 6.9%of patients with tumor size<2 cm.In patients without both endoscopic findings,EUS identified deeper cancer and changed management in 4.8%(1/20)of cases.CONCLUSION EUS was reasonably specific in ruling out submucosal invasion but had relatively poor sensitivity.Data validated endoscopic indicators suggested superficial cancers in the group with a tumor size<2 cm and the lack of esophageal ulceration.In patients with these findings,EUS rarely identified a deep cancer that warranted a change in management.展开更多
MicroRNAs （miRNAs）, which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene （miR-21） has been reported to be highly expressed in various s...MicroRNAs （miRNAs）, which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene （miR-21） has been reported to be highly expressed in various solid tumors, including breast cancer. Bone morphogenetic protein-6 （BMP-6） has been identified as an inhibitor of breast cancer epithelial-mesenchymal transition （EMT） through rescuing E-cadherin expression. We initiated experi- ments to identify the relationships between miR-21 and BMP-6 in breast cancer progression. Real-time PCR analysis showed that miR-21 expression was very high in MDA-MB-231 cells that expressed little BMP-6. A reverse correla- tion between BMP-6 and miR-21 was also determined in breast cancer tissue samples. Moreover, BMP-6 inhibited miR-21 transcription in MDA-MB-231 cells. In order to investigate how BMP-6 inhibited the miR-21 promoter （miPPR-21）, we constructed a series of miPPR-21 reporters. Luciferase assay results indicated that BMP-6 inhibited miPPR-21 activity through the E2-box and AP-l-binding sites. We also demonstrated that both δEF1 and TPA in- duced miR-21 expression. Using site-directed mutation and CHIP assay, we found that δEF1 induced miPPR-21 ac- tivity by binding to the E2-box on miPPR-21. Moreover, TPA triggered miPPR-21 activity through the AP-I binding sites. BMP-6 treatment significantly reduced the binding of these factors to miPPR-21 by decreasing the expression of δEF1 and c-Fos/c-Jun. We also demonstrated that BMP-6-induced downregulation of miR-21 modified the activ- ity of PDCD4 3＇UTR and inhibited MDA-MB-231 cell invasion. δEF1 overexpression and TPA induction blocked this inhibitory effect of BMP-6. In conclusion, BMP-6-induced inhibition of miR-21 suggests that BMP-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of miR-21 in breast cancer.展开更多
Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is...Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.展开更多
AIM: To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.
Objective： To develop and validate a radiomics prediction model for individualized prediction of perineural invasion（PNI） in colorectal cancer（CRC）.Methods： After computed tomography（CT） radiomics features ext...Objective： To develop and validate a radiomics prediction model for individualized prediction of perineural invasion（PNI） in colorectal cancer（CRC）.Methods： After computed tomography（CT） radiomics features extraction, a radiomics signature was constructed in derivation cohort（346 CRC patients）. A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen（CEA） level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation（separate from the cohort used to build the model） was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results： The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell＇s concordance index（c-index）： 0.817; 95% confidence interval（95% CI）： 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination（c-index： 0.803; 95% CI： 0.794–0.812）.Conclusions： Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.展开更多
Narrow band imaging(NBI)is a newly developed technology aiming to provide additional endoscopic information for patients with bladder cancer.This review focuses on the diagnostic accuracy and treatment outcome using N...Narrow band imaging(NBI)is a newly developed technology aiming to provide additional endoscopic information for patients with bladder cancer.This review focuses on the diagnostic accuracy and treatment outcome using NBI cystoscopy for the treatment of nonmuscle invasive bladder cancer.Current results showed improved sensitivity of NBI cystoscopy compared to conventional white light cystoscopy,although lower specificity and increased false-positive results were reported using NBI cystoscopy.The treatment outcome using NBI technology in transurethral resection of bladder tumor had a positive impact while decreased number of residual tumors and tumor recurrence at follow-up were reported.In the future,the application of NBI technology might refine the treatment and follow-up protocol in patients with non-muscle invasive bladder cancer.However,this large scale prospective studies are required to confirm the real cost-effectiveness of this new technology.展开更多
文摘Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in most patients,BCG failure occurs in 30%–50%of patients and a progression to muscle-invasive disease is found in 10%–15%.Therefore,predicting high-risk patients who might not benefit from BCG treatment is critical.The purpose of this study was to identify,whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.Methods:Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into“responders”and“non-responders”groups.Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.Results:Mutations in TP53,FGFR3,PIK3CA,KRAS,CTNNB1,ALK and DDR2 genes were detected.TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort(31.6%and 26.3%,respectively),followed by PIK3CA(15.8%).In the BCG-responsive patient group,90%of samples were found to have mutated genes,with almost 50%of them showing mutations in tyrosine kinase receptors and CTNNB1 genes.On the other hand,in the BCG-unresponsive group,we found mutations in 44.4%of samples,mainly in TP53 gene.Conclusions:Our findings suggest that a Next-Generation Sequencing(NGS)multigene panel is useful in predicting BCG response in patients with NMIBC.
基金supported by the National Natural Science Foundation of China(No.30930038)National"973"Program of China(No.2009CB521700+1 种基金2009CB918903)Program for Changjiang Scholars and Innovative Research Team in University(No.IRT0743)
文摘The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.
基金The National Natural Science Foundation of China(Grant No.81373343 and 81673367)
文摘Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-conjugated epirubicin liposomes by incorporating a synthesized folate-lipid derivative; and to assess the effects on cellular drug uptake, co-localization of drug with nuclei and efficacy in treatment of invasive breast cancer cells. The studies were performed on invasive human breast cancer cells. The folate-PEG2ooo-DSPE conjugate was synthesized, and the constructed folate-conjugated epirubicin liposomes were approximately 1 O0 nm in size. The in vitro studies demonstrated that the folate-conjugated epirubicin liposomes had the strongest cellular drug uptake and co-localization with nuclei of the invasive breast cancer cells. Besides, the liposomes displayed the most significant efficacy in killing the invasive cancer cells, in preventing their invasive potential, and in penetrating ability into breast cancer spheroid as well. In conclusion, the constructed folate-conjugated epirubicin liposomes were able to enhance the efficacy in treatment of invasive breast cancer by improving the cellular drug uptake and increasing the co-localization with nuclei, hence offering a new strategy for potentially eradicating the invasive breast cancer cells.
基金suppor ted by the National Key Research and Development Plan of China(Technology helps Economy 2020,2016YFC0106300)the National Natural Science Foundation of China(82174230)the Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52)。
文摘Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.
基金We thank Dr. Neha Sanwalka for the support with the statisticalanalysis and Dr. Meenal Hastak and Dr. Bijal Kulkarnifor their continued support and in discussion of pathologicalaspects of disease.
文摘Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.
基金The Special Government Funding (EVO) allocated to Turku University Hospitalthe Turku University Foundation, to Avoranta ST+1 种基金the Cancer Society of South-Western Finland, to Sundstrm JTTthe Finnish Society for Therapeutic Radiology and Oncology, to Korkeila EA
文摘AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer. METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as "front-positive" and in 41% as "front-negative". The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the "front-positive" tumors. CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.
文摘Objective:Neoadjuvant chemotherapy followed by radical cystectomy is considered the standard of care for patients with muscle invasive bladder cancer.In the last decade,interest in neoadjuvant chemotherapy has slowly shifted from methotrexate,vinblastine,doxorubicin and cisplatin regime to gemcitabine and cisplatin regime.There are many publications on gemcitabine and cisplatin regime in literature which cover different aspects of treatment.This review aims to summarise the findings published so far on gemcitabine and cisplatin regime and present it in a concise manner.Methods:A systematic literature review was conducted searching the PubMeddatabase in December 2016 using the medical subject heading(MeSH)with the terms gemcitabine,cisplatin,chemotherapy,muscle invasive bladder cancer,and neoadjuvant.All relevant studies were included and results were analysed.Results:A total of 13 studies were included which published between 2007 and 2015.These 13 studies comprised of 754 subjects suffering from muscle invasive bladder cancer.The proportion of male patients ranged from 60%to 86.4%and the median age ranged from 54.2 to 77.3 years in various studies.Complete pathological response(pT0)was seen in 30.0%of patients and pathological downstaging(<pT2)was seen in 48.67%of patients.Conclusion:As per latest guidelines,neoadjuvant chemotherapy is recommended for patients with muscle invasive bladder cancer.There is substantial pathological downstaging with low toxicity in patients of muscle invasive bladder cancer who receive neoadjuvant gemcitabine and cisplatin regime.
文摘Objective:THigh-risk non-invasive bladder cancer(NMIBC)has a high rate of recurrence and disease progression.At present,there are still insufficient effective prevention and treatment methods,especially for patients who have failed BCG treatment.This article reviews the research progress of the molecular mechanism of BCG unresponsive NMIBC,and summarizes the current status and prospects of emerging therapeutic strategies represented by immunotherapy,providing a theoretical basis for the immunotherapy of BCG non-reactive NMIBC.Methods:We searched the PubMed and CNKI journal full-text database search system for keywords"non-muscle invasive bladder cancer,BCG unresponsive,disease recurrence,disease progression,and immunotherapy"with 126 English and 538 Chinese articles.The literature,as well as the relevant clinical research in ClinicalTrials.gov,were integrated together to obtain the results.Results:Immunotherapy was performed in various types of tumors,and the use of immunotherapeutic drugs with different oncotargets administered alone,sequentially or in combination for the treatment of BCG-unresponsive NMIBC have achieved favorable effects,and more Clinical research is still ongoing.Conclusion:Immunotherapy is currently the most promising treatment for cancer,and it is indispensable for patients with NMIBC,both biologically and clinically.We look forward to more laboratory and clinical research in immunotherapy in the future.
文摘The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.
文摘Objectives: Previous reviews reported the outcome of each scientific modality in the management of T1 high-grade bladder cancer. The objective of this review is to assess and evaluate the available scientific modalities used during the last two decades and determine whether they were able to improve the clinical outcome. Literature Search Methodology: A systematic literature review was conducted from 2000-2020 using PubMed, Medline, Embase, and other database sites looking at randomized controlled trials (RCTs), clinical trials, research, review articles, and original articles addressing the different scientific modalities used to diagnose and manage patients with non-muscle invasive Bladder cancer (NMIBC)during the last 2 decades. More than 573 studies were retrieved following the preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and PICOS criteria (Population, Intervention, Comparators, Outcomes, and Study design). Only 85 articles were selected for review including 19 prospective trials, 44 RCTs, original articles, research articles, one review article, and clinical trials—Retrospective studies were excluded to limit bias as much as possible in the analysis. Results: Randomized controlled trials (RCTs) have become the gold standard for evaluating the efficacy of new treatments. They are considered the highest standard of evidence-based medicine and are the method of choice. Overall, we selected 85 studies for review, among them 63 prospective trials and RCTs, with a total of 21,895 patients, published between 2000 and 2020. Previously conducted studies have shown that identifying rare histological types with poor prognoses can help improve outcomes, mainly the plasmacytoid type. Many articles addressed the role of biomarkers in the early identification of patients with NMIBC for recurrence and progression—P-cadherin expression and others were used to predict recurrence and/or progression with promising results. Despite the need for modifications, risk stratification is an important tool that should be used to improve the outcome of patients with NMIBC. Some found that fluorescence diagnostic cystoscopy (FDC) and Photodynamic diagnosis (PDD) improved recurrence-free survival but not progression and outcome. All authors agree that intravesical BCG is the most effective therapy that changes the course of high-grade T1 mainly progression. Re-TURBT has become one of the recommendations of international societies, but its potential effect on survival improvement is debatable. Most of the articles showed the advantages of early cystectomy in NMIBC but all agree that the selection criteria must be clearly defined. Conclusions: This review analyzed the outcomes provided by the scientific advances in the field of management of NMIBC patients in the last two decades. Patients with T1 bladder cancer have variable outcomes because of tumor heterogeneity and clinical staging. Despite the great development in the field of diagnosis, risk stratification, and management, further large studies are mostly needed to better elucidate this subset of patients and avoid over and under-treatment.
文摘BACKGROUND Transcatheter arterial chemoembolization(TACE)is a key treatment approach for advanced invasive liver cancer(infiltrative hepatocellular carcinoma).However,its therapeutic response can be difficult to evaluate accurately using conventional two-dimensional imaging criteria due to the tumor’s diffuse and multifocal growth pattern.Volumetric imaging,especially enhanced tumor volume(ETV),offers a more comprehensive assessment.Nonetheless,bias field inhomogeneity in magnetic resonance imaging(MRI)poses challenges,potentially skewing volumetric measurements and undermining prognostic evaluation.AIM To investigate whether MRI bias field correction enhances the accuracy of volumetric assessment of infiltrative hepatocellular carcinoma treated with TACE,and to analyze how this improved measurement impacts prognostic prediction.METHODS We retrospectively collected data from 105 patients with invasive liver cancer who underwent TACE treatment at the Affiliated Hospital of Xuzhou Medical University from January 2020 to January 2024.The improved N4 bias field correction algorithm was applied to process MRI images,and the ETV before and after treatment was calculated.The ETV measurements before and after correction were compared,and their relationship with patient prognosis was analyzed.A Cox proportional hazards model was used to evaluate prognostic factors,with Martingale residual analysis determining the optimal cutoff value,followed by survival analysis.RESULTS Bias field correction significantly affected ETV measurements,with the corrected baseline ETV mean(505.235 cm^(3))being significantly lower than before correction(825.632 cm^(3),P<0.001).Cox analysis showed that the hazard ratio(HR)for corrected baseline ETV(HR=1.165,95%CI:1.069-1.268)was higher than before correction(HR=1.063,95%CI:1.031-1.095).Using 412 cm^(3) as the cutoff,the group with baseline ETV<415 cm^(3) had a longer median survival time compared to the≥415 cm^(3) group(18.523 months vs 8.926 months,P<0.001).The group with an ETV reduction rate≥41%had better prognosis than the<41%group(17.862 months vs 9.235 months,P=0.006).Multivariate analysis confirmed that ETV reduction rate(HR=0.412,P<0.001),Child-Pugh classification(HR=0.298,P<0.001),and Barcelona Clinic Liver Cancer stage(HR=0.578,P=0.045)were independent prognostic factors.CONCLUSION Volume imaging based on MRI bias field correction can improve the accuracy of evaluating the efficacy of TACE treatment for invasive liver cancer.The corrected ETV and its reduction rate can serve as independent indicators for predicting patient prognosis,providing important reference for developing individualized treatment strategies.
基金Beijing-Tianjin-Hebei Precision Medicine Project of Natural Science Foundation of Hebei Province(H2019104018)and the Science and Technology Bureau of Baoding City(2141ZF261)。
文摘Objective: To explore the diagnostic value of serum tumor markers CEA, AFP, CA199, CA125, CA153, CYFRA21, CA724, and NSE in invasive breast cancer. Methods: A total of 314 patients with invasive breast cancer from Baoding First Central Hospital between January 2021 and December 2022, and 31 patients with benign breast diseases (including mastitis, breast fibroadenoma, breast adenosis, adenoma of the breast, benign phyllodes tumor of the breast, and intraductal papilloma) were randomly selected as the control group. The levels of CEA, AFP, CA199, CA125, CA153, CYFRA21, CA724, and NSE were measured using electrochemiluminescence. Results: The serum concentrations of CEA, CA153, and CYFRA21 showed significant statistical differences between the invasive breast cancer group and the benign breast disease group (P < 0.01). ROC curve analysis revealed that CA153 had the highest sensitivity for diagnosing invasive breast cancer, while CEA had the highest specificity, at 84.4% and 77.4%, respectively. When multiple tumor markers were used for the diagnosis of invasive breast cancer, the combination of CEA and CA153 showed the highest specificity at 90.3%, while the combination of CEA and CYFRA21 had the highest sensitivity at 88.2%. The combined detection of CEA, CYFRA21, and CA153 had the largest area under the curve (AUC) on the ROC curve, at 0.802, indicating that the combination of these three markers provided the best diagnostic performance for invasive breast cancer. Conclusion: CEA, CA153, and CYFRA21 can be used for the diagnosis of invasive breast cancer, and the combined detection of these three markers offers the best diagnostic efficacy for invasive breast cancer.
基金from Red de Investigacion en SIDA(RIS)ART AIDS Foundation+2 种基金Gilead SciencesObra Social Caixa SabadellGala contra la SIDA Barcelona 2011
文摘Invasive-squamous-cell-cancer(ISCC)of the anal canal is an uncommon disease.Human papillomavirus(HPV)is the etiological agent of most of types of ISCC.The incidence of ISCC has been increasing in HIV-infected individuals,even after the introduction of highly active antiretroviral therapy.The aim of this study was to analyze biopsy specimens from patients diagnosed with ISCC at a tertiary hospital from 1983 to 2012 in order to detect HPV-DNA.Methods:Formaldehyde-fixed,paraffin-embedded specimens from patients with ISCC underwent HPV-DNA genotyping using multiplex PCR assay.Results:A total of 31 cases were collected;10 were HIV-infected(9 men,1 woman)and 21 non-HIV-infected(11 men,10 women).HPV infection was detected in 87.5%(7/8)of the HIV-infected patients(DNA from 2 biopsies was degraded)and 76.2%(16/21)of non-HIV-infected individuals.Multiple-type infections were only found in 28.6%(2/7)of the HIV-infected patients(no multiple-type infections in non-HIV-infected individuals).The most prevalent type was HPV-16:50%(4/8)in the HIV-infected group(57%[4/7]of the HPV-positive samples)and 66.7%(14/21)in the non-HIV-infected group(87.5%(14/16)of the HPV-positive samples).Remarkably,37.5%(3/8)of the HIV-infected group had high-risk HPV types not included in the vaccines(HPV-33,51,52,and 66)compared with 4.8%in the non-HIV-infected group(1/21,HPV-52).All cases of anal ISCC in HIV-infected patients were recorded in the highly active antiretroviral therapy era.Conclusion:HIV-infected patients presented anal ISCC with a higher proportion of high-risk HPV types not covered by the conventional vaccines than non-HIV-infected individuals.
文摘Objective To assess the feasibility and clinical efficacy of minimally invasive esophagectomy for esophageal cancer. Methods From July 2007 to December 2009,eighty-one patients with esophageal cancer received combined thoracoscopic and laparoscopic esophagectomy with anastomosis in the neck. All clinical data were retrospectively reviewed. Results The median operative
文摘BACKGROUND Endoscopic ultrasound(EUS)stands as an accurate imaging modality for esophageal cancer staging,however utilization of EUS in early-stage cancer management remains controversial.Identification of non-applicability of endoscopic interventions with deep muscular invasion with EUS in pre-intervention evaluation of early-stage esophageal cancer is compared to endoscopic and histologic indicators.AIM To display the role of EUS in pre-intervention early esophageal cancer staging and how the index endoscopic features of invasive esophageal malignancy compare for prediction of depth of invasion and cancer management.METHODS This was a retrospective study of patients who underwent pre-resection EUS after a diagnosis of esophageal cancer at a tertiary medical center from 2012 to 2022.Patient clinical data,initial esophagogastroduodenoscopy/biopsy,EUS,and final resection pathology reports were abstracted,and statistical analysis was conducted to assess the role of EUS in management decisions.RESULTS Forty nine patients were identified for this study.EUS T stage was concordant with histological T stage in 75.5%of patients.In determining submucosal involvement(T1a vs T1b),EUS had a specificity of 85.0%,sensitivity of 53.9%,and accuracy of 72.7%.Endoscopic features of tumor size>2 cm and the presence of esophageal ulceration were significantly associated with deep invasion of cancer on histology.EUS affected management from endoscopic mucosal resection/submucosal dissection to esophagectomy in 23.5%of patients without esophageal ulceration and 6.9%of patients with tumor size<2 cm.In patients without both endoscopic findings,EUS identified deeper cancer and changed management in 4.8%(1/20)of cases.CONCLUSION EUS was reasonably specific in ruling out submucosal invasion but had relatively poor sensitivity.Data validated endoscopic indicators suggested superficial cancers in the group with a tumor size<2 cm and the lack of esophageal ulceration.In patients with these findings,EUS rarely identified a deep cancer that warranted a change in management.
文摘MicroRNAs （miRNAs）, which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene （miR-21） has been reported to be highly expressed in various solid tumors, including breast cancer. Bone morphogenetic protein-6 （BMP-6） has been identified as an inhibitor of breast cancer epithelial-mesenchymal transition （EMT） through rescuing E-cadherin expression. We initiated experi- ments to identify the relationships between miR-21 and BMP-6 in breast cancer progression. Real-time PCR analysis showed that miR-21 expression was very high in MDA-MB-231 cells that expressed little BMP-6. A reverse correla- tion between BMP-6 and miR-21 was also determined in breast cancer tissue samples. Moreover, BMP-6 inhibited miR-21 transcription in MDA-MB-231 cells. In order to investigate how BMP-6 inhibited the miR-21 promoter （miPPR-21）, we constructed a series of miPPR-21 reporters. Luciferase assay results indicated that BMP-6 inhibited miPPR-21 activity through the E2-box and AP-l-binding sites. We also demonstrated that both δEF1 and TPA in- duced miR-21 expression. Using site-directed mutation and CHIP assay, we found that δEF1 induced miPPR-21 ac- tivity by binding to the E2-box on miPPR-21. Moreover, TPA triggered miPPR-21 activity through the AP-I binding sites. BMP-6 treatment significantly reduced the binding of these factors to miPPR-21 by decreasing the expression of δEF1 and c-Fos/c-Jun. We also demonstrated that BMP-6-induced downregulation of miR-21 modified the activ- ity of PDCD4 3＇UTR and inhibited MDA-MB-231 cell invasion. δEF1 overexpression and TPA induction blocked this inhibitory effect of BMP-6. In conclusion, BMP-6-induced inhibition of miR-21 suggests that BMP-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of miR-21 in breast cancer.
基金Supported by Grants (No. S0801035, to Naito Z) from the Ministry of Education, Culture, Sports, Science, and Technol-ogy (MEXT), JapanGrant-in-Aid for Young Scientists (A, No. 22689038 to Matsuda Y)
文摘Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.
基金Supported by The "Eleventh Five-year Plan" for Medical Sci-ence Development of PLA,No.06MB243the National Natural Science Foundation of China,No.81101101 and No.51273165+1 种基金the Key Project of Chinese Ministry of Education,No.212149the Projects of Sichuan Province,No.2010SZ0294,No.2011JQ0032 and No.12ZB038
文摘AIM: To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.
基金supported by the National Key Research and Development Program of China (No. 2017YFC1309100)the National Natural Scientific Foundation of China (No. 81771912, 81701782 and 81601469)
文摘Objective： To develop and validate a radiomics prediction model for individualized prediction of perineural invasion（PNI） in colorectal cancer（CRC）.Methods： After computed tomography（CT） radiomics features extraction, a radiomics signature was constructed in derivation cohort（346 CRC patients）. A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen（CEA） level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation（separate from the cohort used to build the model） was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results： The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell＇s concordance index（c-index）： 0.817; 95% confidence interval（95% CI）： 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination（c-index： 0.803; 95% CI： 0.794–0.812）.Conclusions： Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.
文摘Narrow band imaging(NBI)is a newly developed technology aiming to provide additional endoscopic information for patients with bladder cancer.This review focuses on the diagnostic accuracy and treatment outcome using NBI cystoscopy for the treatment of nonmuscle invasive bladder cancer.Current results showed improved sensitivity of NBI cystoscopy compared to conventional white light cystoscopy,although lower specificity and increased false-positive results were reported using NBI cystoscopy.The treatment outcome using NBI technology in transurethral resection of bladder tumor had a positive impact while decreased number of residual tumors and tumor recurrence at follow-up were reported.In the future,the application of NBI technology might refine the treatment and follow-up protocol in patients with non-muscle invasive bladder cancer.However,this large scale prospective studies are required to confirm the real cost-effectiveness of this new technology.
