BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identif...BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.展开更多
Purpose: This study focused on maintaining and improving the walking function of late-stage older individuals while longitudinally tracking the effects of regular exercise programs in a day-care service specialized fo...Purpose: This study focused on maintaining and improving the walking function of late-stage older individuals while longitudinally tracking the effects of regular exercise programs in a day-care service specialized for preventive care over 5 years, using detailed gait function measurements with an accelerometer-based system. Methods: Seventy individuals (17 male and 53 female) of a daycare service in Tokyo participated in a weekly exercise program, meeting 1 - 2 times. The average age of the participants at the start of the program was 81.4 years. Gait function, including gait speed, stride length, root mean square (RMS) of acceleration, gait cycle time and its standard deviation, and left-right difference in stance time, was evaluated every 6 months. Results: Gait speed and stride length improved considerably within six months of starting the exercise program, confirming an initial improvement in gait function. This suggests that regular exercise programs can maintain or improve gait function even age groups that predictably have a gradual decline in gait ability due to enhanced age. In the long term, many indicators tended to approach baseline values. However, the exercise program seemingly counteracts age-related changes in gait function and maintains a certain level of function. Conclusions: While a decline in gait ability with aging is inevitable, establishing appropriate exercise habits in late-stage older individuals may contribute to long-term maintenance of gait function.展开更多
Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. M...Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. Methods: Thirty-two late-stage elderly individuals were evaluated for knee pain during rest, walking, and program exercises, with and without TENS. Gait analysis was performed using an IoT-based gait analysis device to examine the effects of TENS-induced analgesia on gait. Results: TENS significantly reduced knee pain during rest, walking, and programmed exercises, with the greatest analgesic effect observed during walking. The greater the knee pain without TENS, the more significant the analgesic effect of TENS. A comparison of gait parameters revealed a significant difference only in the gait cycle time, with a trend towards faster walking with TENS;however, the effect was limited. Conclusion: TENS effectively relieves knee pain in late-stage elderly individuals and can be safely applied during exercise. Pain management using TENS provides important insights into the implementation of exercise therapy in this age group.展开更多
New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individua...New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.展开更多
BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of...BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.展开更多
AIM:To determine the optimal type of surgery for latestage gastric cancer with hepatic metastases.METHODS:We retrospectively analyzed 49 gastrectomies for late-stage gastric cancer conducted in the FirstHospital Affil...AIM:To determine the optimal type of surgery for latestage gastric cancer with hepatic metastases.METHODS:We retrospectively analyzed 49 gastrectomies for late-stage gastric cancer conducted in the FirstHospital Affiliated to Henan University of Science and Technology between September 2003 and September 2010.All gastrectomy operations were divided into two groups:radical resection(gastrectomy and simultaneous resection of hepatic metastases,n =31),and palliative resection(gastrectomy without hepatic resection,n =18).All 49 patients had chemotherapy catheter implantation in the hepatic artery via the gastroduodenal artery.Postoperative complications and cumulative survival rates of the two groups were compared and analyzed.RESULTS:There was no significant difference in the number of perioperative complications between the radical and palliative resection groups(6 and 3 cases,respectively,P > 0.05).The incidence of long-term complications including ileus(3 in the radical resection and 2 in the palliative resection groups) and anastomosis(2 cases in each group) was not significantly different(P > 0.05).The cumulative survival rate was significantly lower in the palliative resection group(P < 0.05).CONCLUSION:Radical gastrectomy with resection of hepatic metastases and hepatoarterial catheter implantation is the recommended surgery for late-stage gastric cancer patients with hepatic metastases.展开更多
Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three y...Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial treatment.The median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 mo.mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor development.CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations.Different genomic and nongenomic events can induce subclone diversity,which leads to cancer and metastasis.Throughout the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular functions.However,cancer cells presenting neoantigens can be recognized and eliminated by the immune system.In this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle factors.Despite remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains unclear.This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.展开更多
Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well orga...Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well organized,has succeeded in reducing the incidence of colon and rectal cancer and improving the prognosis related to them.Despite considerable advancements in screening technologies and strategies,the effectiveness of CRC screening programs remains less than optimal.This paper examined the multifaceted reasons behind the persistent lack of effect-iveness in CRC screening initiatives.Through a critical analysis of current methodologies,technological limitations,patient-related factors,and systemic challenges,we elucidated the complex interplay that hampers the successful reduction of CRC morbidity and mortality rates.While acknowledging the ad-vancements that have improved aspects of screening,we emphasized the necessity of addressing the identified barriers comprehensively.This study aimed to raise awareness of how important CRC screening is in reducing costs for this disease.Screening and early diagnosis are not only important in improving the prognosis of patients with CRC but can lead to an important reduction in the cost of treating a disease that is often diagnosed at an advanced stage.Spending more sooner can mean saving money later.展开更多
BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of ...BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.展开更多
Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in scree...Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.展开更多
The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of ...The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of those affected are diagnosed later,in advanced stages.The efficacy of screening programs has been well-established for several years,which reduces the risk of CRC morbidity and mortality,without taking into account the test used for screening,or other tools.Nevertheless,a significant proportion of patients remain unscreened,so understanding the factors involved,as well as the barriers of the population to adherence is the first step to possibly modify the participation rate.These barriers could include a full range of social and political aspects,especially the type of financial provision of each health service.In Japan,health services are universal,and this advantageous situation makes it easier for citizens to access to these services,contributing to the detection of various diseases,including CRC.Interestingly,the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities,and symptomatic and cancer screening groups showed similar early-stage diagnosis.展开更多
Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the m...Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.展开更多
Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of im...Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.展开更多
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC...BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.展开更多
Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichme...Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.展开更多
BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methy...BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expression led to cisplatin resistance.CONCLUSION METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.展开更多
BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been pr...BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.展开更多
BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for indivi...BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive performance.In the training and internal and external validation groups,the AUCs of the CR model were 0.889(95%CI:0.824-0.954),0.889(95%CI:0.803-0.976)and 0.894(95%CI:0.814-0.974).Delong test,NRI,and IDI showed that the CR model had significant differences from other models(P<0.05).Calibration curves demonstrated good agreement,and DCA revealed significant benefits of the CR model.CONCLUSION The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively,which facilitates individualized treatment of RC patients.展开更多
Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of n...Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new cases worldwide and 48.6% of global deaths attributed to this malignancy~1.展开更多
基金Supported by the National Natural Science foundation of China,No.82202135,82371919,82372017,and 82171925China Postdoctoral Science Foundation,No.2023M741808+3 种基金Young Elite Scientists Sponsorship Program by Jiangsu Association for Science and Technology,No.JSTJ-2023-WJ027Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine,No.2023QB0112Nanjing Postdoctoral Science Foundation,Natural Science Foundation of Nanjing University of Chinese Medicine,No.XZR2023036 and XZR2021050Medical Imaging Artificial Intelligence Special Research Fund Project,Nanjing Medical Association Radiology Branch,Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province,China,No.JD2023SZ16.
文摘BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.
文摘Purpose: This study focused on maintaining and improving the walking function of late-stage older individuals while longitudinally tracking the effects of regular exercise programs in a day-care service specialized for preventive care over 5 years, using detailed gait function measurements with an accelerometer-based system. Methods: Seventy individuals (17 male and 53 female) of a daycare service in Tokyo participated in a weekly exercise program, meeting 1 - 2 times. The average age of the participants at the start of the program was 81.4 years. Gait function, including gait speed, stride length, root mean square (RMS) of acceleration, gait cycle time and its standard deviation, and left-right difference in stance time, was evaluated every 6 months. Results: Gait speed and stride length improved considerably within six months of starting the exercise program, confirming an initial improvement in gait function. This suggests that regular exercise programs can maintain or improve gait function even age groups that predictably have a gradual decline in gait ability due to enhanced age. In the long term, many indicators tended to approach baseline values. However, the exercise program seemingly counteracts age-related changes in gait function and maintains a certain level of function. Conclusions: While a decline in gait ability with aging is inevitable, establishing appropriate exercise habits in late-stage older individuals may contribute to long-term maintenance of gait function.
文摘Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. Methods: Thirty-two late-stage elderly individuals were evaluated for knee pain during rest, walking, and program exercises, with and without TENS. Gait analysis was performed using an IoT-based gait analysis device to examine the effects of TENS-induced analgesia on gait. Results: TENS significantly reduced knee pain during rest, walking, and programmed exercises, with the greatest analgesic effect observed during walking. The greater the knee pain without TENS, the more significant the analgesic effect of TENS. A comparison of gait parameters revealed a significant difference only in the gait cycle time, with a trend towards faster walking with TENS;however, the effect was limited. Conclusion: TENS effectively relieves knee pain in late-stage elderly individuals and can be safely applied during exercise. Pain management using TENS provides important insights into the implementation of exercise therapy in this age group.
文摘New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.
基金the Foundation for Cancer Research supported by Kyoto Preventive Medical Center and the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid KAKENHI,No.JP 22K21080.
文摘BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.
文摘AIM:To determine the optimal type of surgery for latestage gastric cancer with hepatic metastases.METHODS:We retrospectively analyzed 49 gastrectomies for late-stage gastric cancer conducted in the FirstHospital Affiliated to Henan University of Science and Technology between September 2003 and September 2010.All gastrectomy operations were divided into two groups:radical resection(gastrectomy and simultaneous resection of hepatic metastases,n =31),and palliative resection(gastrectomy without hepatic resection,n =18).All 49 patients had chemotherapy catheter implantation in the hepatic artery via the gastroduodenal artery.Postoperative complications and cumulative survival rates of the two groups were compared and analyzed.RESULTS:There was no significant difference in the number of perioperative complications between the radical and palliative resection groups(6 and 3 cases,respectively,P > 0.05).The incidence of long-term complications including ileus(3 in the radical resection and 2 in the palliative resection groups) and anastomosis(2 cases in each group) was not significantly different(P > 0.05).The cumulative survival rate was significantly lower in the palliative resection group(P < 0.05).CONCLUSION:Radical gastrectomy with resection of hepatic metastases and hepatoarterial catheter implantation is the recommended surgery for late-stage gastric cancer patients with hepatic metastases.
文摘Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial treatment.The median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 mo.mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor development.CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations.Different genomic and nongenomic events can induce subclone diversity,which leads to cancer and metastasis.Throughout the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular functions.However,cancer cells presenting neoantigens can be recognized and eliminated by the immune system.In this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle factors.Despite remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains unclear.This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.
文摘Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well organized,has succeeded in reducing the incidence of colon and rectal cancer and improving the prognosis related to them.Despite considerable advancements in screening technologies and strategies,the effectiveness of CRC screening programs remains less than optimal.This paper examined the multifaceted reasons behind the persistent lack of effect-iveness in CRC screening initiatives.Through a critical analysis of current methodologies,technological limitations,patient-related factors,and systemic challenges,we elucidated the complex interplay that hampers the successful reduction of CRC morbidity and mortality rates.While acknowledging the ad-vancements that have improved aspects of screening,we emphasized the necessity of addressing the identified barriers comprehensively.This study aimed to raise awareness of how important CRC screening is in reducing costs for this disease.Screening and early diagnosis are not only important in improving the prognosis of patients with CRC but can lead to an important reduction in the cost of treating a disease that is often diagnosed at an advanced stage.Spending more sooner can mean saving money later.
基金This study has been reviewed and approved by the Clinical Medical Ethics Committee(Approval No.2021HN26A).
文摘BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.
文摘Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.
文摘The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of those affected are diagnosed later,in advanced stages.The efficacy of screening programs has been well-established for several years,which reduces the risk of CRC morbidity and mortality,without taking into account the test used for screening,or other tools.Nevertheless,a significant proportion of patients remain unscreened,so understanding the factors involved,as well as the barriers of the population to adherence is the first step to possibly modify the participation rate.These barriers could include a full range of social and political aspects,especially the type of financial provision of each health service.In Japan,health services are universal,and this advantageous situation makes it easier for citizens to access to these services,contributing to the detection of various diseases,including CRC.Interestingly,the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities,and symptomatic and cancer screening groups showed similar early-stage diagnosis.
基金funded by the National Natural Science Foundation of China(82003879)Project of Science and Technology Department of Sichuan Province(2023NSFSC1928,2023NSFSC1992)+3 种基金Young Elite Scientists Sponsorship Program China Association for Science and Technology(CACM-2020-QNRC1-01)Project of State Administration of Traditional Chinese Medicine of China(ZYYCXTD-D-202209)Project of Undergraduate Training Programs for Innovation and Entrepreneurship(S202310610637)the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(SKLTCM202205).
文摘Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.
基金supported by grants from the National Natural Science Foundation of China (Grant No. U20A20369)GuangDong Basic and Applied Basic Research Foundation (Grant No. 2022B1515120085)。
文摘Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
基金Supported by the Songjiang District Tackling Key Science and Technology Research Projects,No.20sjkjgg32Excellent Young Talents Training Program of Songjiang Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,No.QNRC-004Science and Technology project of Songjiang District,No.22SJKJGG81.
文摘BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.
基金supported by grants from the Health Commission of Henan Province(Grant No.SBGJ20211008)the Henan Provincial Department of Science and Technology(Grant No.222300420574)。
文摘Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.
文摘BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expression led to cisplatin resistance.CONCLUSION METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.
基金Supported by Suzhou Science and Technology Project,No.SYS2019053.
文摘BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.
文摘BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive performance.In the training and internal and external validation groups,the AUCs of the CR model were 0.889(95%CI:0.824-0.954),0.889(95%CI:0.803-0.976)and 0.894(95%CI:0.814-0.974).Delong test,NRI,and IDI showed that the CR model had significant differences from other models(P<0.05).Calibration curves demonstrated good agreement,and DCA revealed significant benefits of the CR model.CONCLUSION The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively,which facilitates individualized treatment of RC patients.
基金supported by The National Key Research and Development Program of China(2021YFA0910100)Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer(JBZX-202006)+4 种基金Medical Science and Technology Project of Zhejiang Province(WKJ-ZJ-2202 and WKJ-ZJ-2104)the National Natural Science Foundation of China(82074245,81973634, and 81903842)Natural Science Foundation of Zhejiang Province(LR21H280001)Science and Technology Projects of Zhejiang Province(2019C03049)Program of Zhejiang Provincial TCM Sci-tech Plan(2018ZY006 and 2020ZZ005)。
文摘Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new cases worldwide and 48.6% of global deaths attributed to this malignancy~1.