Role of tumor-associated macrophages in common digestive system malignant tumors

Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.

Insights into the history and tendency of glycosylation and digestive system tumor:A bibliometric-based visual analysis

BACKGROUND Glycosylation,a commonly occurring post-translational modification,is highly expressed in several tumors,specifically in those of the digestive system,and plays a role in various cellular pathophysiological mechanisms.Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years,bibliometric analysis of this field remains scarce.The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors.AIM To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors.METHODS We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace(version 6.1.R6)to perform bibliometric analysis.RESULTS A total of 2042 documents spanning from 1978 to the present were analyzed,with the research process divided into three phases:the period of obscurity(1978-1990),continuous development period(1991-2006),and the rapid outbreak period(2007-2023).These documents were authored by researchers from 66 countries or regions,with the United States and China leading in terms of publication output.Reis Celso A had the highest number of publications,while Pinho SS was the most cited author.Co-occurrence analysis revealed the most popular keywords in this field are glycosylation,expression,cancer,colorectal cancer,and pancreatic cancer.Furthermore,the Journal of Proteome Research was the most prolific journal in terms of publications,while the Journal of Biological Chemistry had the most citations.CONCLUSION The bibliometric analysis shows current research focus is primarily on basic research in this field.However,future research should aim to utilize glycosylation as a target for treating tumor patients.

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation

Chronic inflammation,through a variety of mechanisms,plays a key role in the occurrence and development of digestive system malignant tumors(DSMTs).In this study,we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation.The development and evaluation of cancer prevention strategies is a longstanding process.Cancer prevention,especially in the early stage of life,should be emphasized throughout the whole life course.Issues such as the time interval for colon cancer screening,the development of direct-acting antiviral drugs for liver cancer,and the Helicobacter pylori vaccine all need to be explored in long-term,large-scale experiments in the future.

Analysis of the rule of medication of compound Chinese traditional patent medicine for digestive system tumors based on data mining

Objective:Based on the data mining method,explore the medication rules of Chinese patent medicines for the treatment of digestive system tumors.Method:Based on the"Chinese Traditional Medicine Prescription Database"in https://db.yaozh.com/,collect Chinese patent medicines for the treatment of digestive system tumors,establish an Excel table,and use the ancient and modern medical case cloud platform(V2.2.1)to perform frequency statistics,association rules,and drugs on the data Clustering and complex network analysis.Results:A total of 36 Chinese patent medicines for the treatment of digestive system tumors were screened.The medicinal properties were mainly warm and cold,the taste was bitter and sweet,and the meridians were mainly liver and spleen meridians.High frequency Chinese medicine include Astragalus,Scutellaria-barbata,Ginseng,Curcuma,Triangle,Atractylodes,Hedyotis diffusa,etc.Correlation analysis obtained 17 drug combinations,High-frequency drug pairs include Scutellaria-barbata-Astragalus,Ginseng-Astragalus,Curcuma-Astragalus,Scutellaria-barbata-Curcuma,etc.Cluster analysis found 3 types of drugs.The core drug network is composed of 27 drugs,and the core compatibility network consists of 3 groups of drugs.Conclusion:The Chinese patent compound medicine for the treatment of digestive system tumors has the characteristics of combining cold and warming,replenishing and reducing treatment,and treating the liver and spleen at the same time.The medicine is mainly used to replenish qi and invigorate the spleen,promote blood circulation and remove blood stasis,and clear away heat and detoxification.Replenish qi,nourish yin,invigorate blood,and detoxify are mainly compatible with each other,reflecting the pathogenesis characteristics of"deficiency,stasis,and toxin"in digestive system tumors.Data mining can provide references for the prescription and compatibility of Chinese patent medicines.

Role of inositol polyphosphate-4-phosphatase type II in oncogenesis of digestive system tumors

Inositol polyphosphate-4-phosphatase type II(INPP4B)is a newly discovered PI(3,4,5)P3 phosphatase.Many studies have revealed that INPP4B is upregulated or downregulated in tumors of the digestive system,and the abnormal expression of INPP4B may be attributed to the occurrence,development,and prognosis of tumors of the digestive system.This paper reviews studies on the correlations between INPP4B and digestive system tumors and the roles of INPP4B in the development of different tumors to provide a theoretical basis for further research on its molecular mechanism and clinical application."INPP4B"and"tumor"were searched as key words in PubMed and in the CNKI series full text database retrieval system from January 2000 to August 2023.A total of 153 Englishlanguage studies and 30 Chinese-language studies were retrieved.The following enrollment criteria were applied:(1)Studies contained information on the biological structure and functions of INPP4B;(2)studies covered the influence of abnormal expression of INPP4B in digestive system tumors;and(3)studies covered the role of INPP4B in the diagnosis,treatment,and prognosis of digestive system tumors.After excluding the literature irrelevant to this study,61 papers were finally included in the analysis.INPP4B expression is low in gastric cancer,colon cancer,pancreatic cancer,and liver cancer but it has high expression in esophageal cancer,colon cancer,pancreatic cancer,and gallbladder cancer.INPP4B is involved in the occurrence and development of digestive system tumors through the regulation of gene expression and signal transduction.The abnormal expression of INPP4B plays an important role in the development of digestive system tumors.Studies on INPP4B provide new molecular insights for the diagnosis,treatment,and prognosis evaluation of digestive system tumors.

IGF2BPs: a family as diagnostic and prognostic biomarkers in digestive system tumors

The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor research.We use bioinformatics methods to explore potential biomarkers of the digestive system.Mining and analyzing data from Gene Expression Profiling Interactive Analysis(GEPIA),Kaplan-Meier,cBioPortal,and Metabolic gEne RApid Visualizer(MERAV)to explore the correlation between IGF2BP(insulin-like growth factor-2 mRNA-binding protein)family expression and immune infiltration in digestive system tumors,and further probe the prognostic value of IGF2BP family in digestive system tumors.Esophageal cancer tissues showed a significantly higher expression of IGF2BP2 than normal tissues,while IGF2BP3 was notably more expressed in esophageal cancer,pancreatic cancer,and stomach cancer.In the prognosis evaluation,the IGF2BP1 gene in patients with liver cancer and the IGF2BP2 and IGF2BP3 genes in patients with stomach cancer and liver cancer of the low gene expression level groups were better.Multivariate COX regression analysis further suggested that tumor stage,CD8 positive T cells,macrophages,dendritic cell infiltration,and IGF2BP3 expression were independent risk factors affecting the prognosis of patients with stem cell liver cancer.The IGF2BP family may be a potential marker for immunotherapy and the prognosis of digestive system tumors.

Clinical study of ultrasound and microbubbles for enhancing chemotherapeutic sensitivity of malignant tumors in digestive system

Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index （MI） in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles （SonoVue） to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 （CTCAE V4.03）. Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.Results： All the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease （SD）, and one patient had a partial response （PR） after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.Conclusions： Our preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.

High incidence combination of multiple primary malignant tumors of the digestive system

BACKGROUND Clinical reports of multiple primary malignant tumors(MPMTs)in the digestive system are increasing.In China,although the survival rate of patients with MPMTs is increasing,the quality of life is very low.Many patients have reached the advanced stage when the second primary tumor is found,resulting in no early intervention and treatment.This is due to the misunderstanding of MPMTs by clinicians,who treat such tumors as metastases.Therefore,before a patient has a second primary tumor,doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient.AIM To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization.METHODS A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively.They were divided into metachronous MPMT and synchronous MPMT groups,and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted.Sex and age differences between metachronous and synchronous tumors were tested by the chi square test and t test,respectively.A P value<0.05 was considered as statistically significant,and SPSS version 26.0(SPSS Inc.,Chicago,Illinois,United States)was used for statistical analysis.RESULTS Among the 1902 patients with MPMTs confirmed by pathology,1811(95.2%)cases were secondary primary cancers,89(4.7%)cases were tertiary primary cancers,and 2(0.1%)cases were quaternary primary cancers.Most(88.2%)of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer.The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows:Breast cancer,thyroid cancer,nonuterine cancer,lung cancer,colon cancer,kidney cancer,uterine cancer,bladder cancer,rectal cancer,and gastric cancer.The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer(11.6%),the highest incidence rate of the second primary cancer was still lung cancer(24.9%),the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer(32.7%),and the highest incidence rate of the second primary cancer was lung cancer(20.8%).Among them,breast cancer,nonuterine cancer and uterine cancer were female-specific malignant tumor types,and thyroid cancer also accounted for 79.6%of female patients.The top five metachronous cancer combinations,independent of female-specific malignant tumor types and thyroid cancer,were colon cancer and lung cancer(26 cases),kidney cancer and lung cancer(25 cases),rectal cancer and lung cancer(20 cases),gastric cancer and lung cancer(17 cases),and bladder cancer and lung cancer(17 cases).The most common synchronous cancer combination was colon cancer and rectal cancer(15 cases).CONCLUSION Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

Clinicopathological significance and prognostic value of claudin10 expression in primary malignant tumors of digestive system:A metaanalysis

Objective:To investigate the correlation between claudin10 expression and clinicopathological characteristics and prognosis of primary malignant tumors of digestive system.Methods:We searched the PubMed,Web of Science,Ovid MEDLINE,CNKI,CQVIP,and WanFang Data databases.The data between claudin10 expression and clinical characteristics as well as survival outcome were extracted.RevMan 5.3 and Stata 15.1 software were employed for metaanalysis.Results:A total of 6 studies containing 512 patients with primary malignant tumors of digestive system were analyzed.The analysis showed that high expression of claudin10 was more common in cancer tissue than in normal tissue[OR=3.22,95%CI(2.26,4.60),P<0.01],and was associated with increasing tumor size[OR=6.21,95%CI(2.44,15.83),P<0.01],high differentiation[OR=0.56,95%CI(0.32,0.99),P=0.05],positive lymph node metastasis[OR=3.41,95%CI(1.09,10.65),P=0.03].The expression of claudin10 was not associated with sex[OR=1.62,95%CI(0.91,2.90),P=0.10],age[OR=1.72,95%CI(0.97,3.07),P=0.06],distant metastasis[OR=4.51,95%CI(0.55,36.70),P=0.16],or prognosis[HR=1.99,95%CI(0.93,4.23),P=0.08].Conclusion:The expression of claudin10 is correlated with the clinicopathological features of primary malignant tumors of digestive system and is a potential tumor marker.

Functions and mechanisms of chemokine receptor 7 in tumors of the digestive system

Chemokine(C-X-C motif)receptor 7(CXCR7),recently termed ACKR3,belongs to the G protein-coupled cell surface receptor family,binds to stromal cellderived factor-1[SDF-1,or chemokine(C-X-C motif)ligand 12]or chemokine(CX-C motif)ligand 11,and is the most common chemokine receptor expressed in a variety of cancer cells.SDF-1 binds to its receptor chemokine(C-X-C motif)receptor 4(CXCR4)and regulates cell proliferation,survival,angiogenesis and migration.In recent years,another new receptor for SDF-1,CXCR7,has been discovered,and CXCR7 has also been found to be expressed in a variety of tumor cells and tumor-related vascular endothelial cells.Many studies have shown that CXCR7 can promote the growth and metastasis of a variety of malignant tumor cells.Unlike CXCR4,CXCR7 exhibits a slight modification in the DRYLAIV motif and does not induce intracellular Ca^2+release following ligand binding,which is essential for recruiting and activating G proteins.CXCR7 is generally thought to work in three ways:(1)Recruitingβ-arrestin 2;(2)Heterodimerizing with CXCR4;and(3)Acting as a“scavenger”of SDF-1,thus lowering the level of SDF-1 to weaken the activity of CXCR4.In the present review,the expression and role of CXCR7,as well as its prognosis in cancers of the digestive system,were investigated.

Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors

The treatment of digestive system tumors presents challenges,particularly in immunotherapy,owing to the advanced immune tolerance of the digestive system.Nanomaterials have emerged as a promising approach for addressing these challenges.They provide targeted drug delivery,enhanced permeability,high bioavailability,and low toxicity.Additionally,nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment(TIME).Among the various cells in the TIME,tumor-associated macrophages(TAMs)are the most abundant and play a crucial role in tumor progression.Therefore,investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance.Here,we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer,colorectal cancer,hepatocellular carcinoma,and pancreatic cancer.We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system.Furthermore,this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors.Overall,this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.

Solid pseudopapillary tumor of the pancreas:A systematic review of clinical,surgical and oncological characteristics of 1384 patients underwent pancreatic surgery

Background:Pancreatic solid pseudopapillary tumors(SPTs)are rare clinical entity,with low malignancy and still unclear pathogenesis.They account for less than 2%of exocrine pancreatic neoplasms.This study aimed to perform a systematic review of the main clinical,surgical and oncological characteristics of pancreatic SPTs.Data sources:MEDLINE/PubMed,Web of Science and Scopus databases were systematically searched for the main clinical,surgical and oncological characteristics of pancreatic SPTs up to April 2021,in accordance with the preferred reporting items for systematic reviews and meta-analyses(PRISMA)standards.Primary endpoints were to analyze treatments and oncological outcomes.Results:A total of 823 studies were recorded,86 studies underwent full-text reviews and 28 met inclusion criteria.Overall,1384 patients underwent pancreatic surgery.Mean age was 30 years and 1181 patients(85.3%)were female.The most common clinical presentation was non-specific abdominal pain(52.6%of cases).Mean overall survival was 98.1%.Mean recurrence rate was 2.8%.Mean follow-up was 4.2 years.Conclusions:Pancreatic SPTs are rare,and predominantly affect young women with unclear pathogenesis.Radical resection is the gold standard of treatment achieving good oncological impact and a favorable prognosis in a yearly life-long follow-up.

Ovarian-adnexal reporting and data system ultrasound evaluation and pathological characteristics of ovarian collision tumor

BACKGROUND Collision tumor are neoplasms,including two histologically distinct tumors that coexist in the same mass without histological admixture.The incidence of collision tumor is low and is rare clinically.AIM To investigate ultrasound images and application of ovarian-adnexal reporting and data system(O-RADS)to evaluate the risk and pathological characteristics of ovarian collision tumor.METHODS This study retrospectively analyzed 17 cases of ovarian collision tumor diagnosed pathologically from January 2020 to December 2023.All clinical features,ultrasound images and histopathological features were collected and analyzed.The O-RADS score was used for classification.The O-RADS score was determined by two senior doctors in the gynecological ultrasound group.Lesions with O-RADS score of 1-3 were classified as benign tumors,and lesions with O-RADS score of 4 or 5 were classified as malignant tumors.RESULTS There were 17 collision tumors detected in 16 of 6274 patients who underwent gynecological surgery.The average age of 17 women with ovarian collision tumor was 36.7 years(range 20-68 years),in whom,one occurred bilaterally and the rest occurred unilaterally.The average tumor diameter was 10 cm,of which three were 2-5 cm,11 were 5-10 cm,and three were>10 cm.Five(29.4%)tumors with O-RADS score 3 were endometriotic cysts with fibroma/serous cystadenoma,and unilocular or multilocular cysts contained a small number of parenchymal components.Eleven(64.7%)tumors had an O-RADS score of 4,including two in category 4A,six in category 4B,and three in category 4C;all of which were multilocular cystic tumors with solid components or multiple papillary components.One(5.9%)tumor had an O-RADS score of 5.This case was a solid mass,and a small amount of pelvic effusion was detected under ultrasound.The pathology was high-grade serous cystic cancer combined with cystic mature teratoma.There were nine(52.9%)tumors with elevated serum carbohydrate antigen(CA)125 and two(11.8%)with elevated serum CA19-9.Histological and pathological results showed that epithelial-cell-derived tumors combined with other tumors were the most common,which was different from previous results.CONCLUSION The ultrasound images of ovarian collision tumor have certain specificity,but diagnosis by preoperative ultrasound is difficult.The combination of epithelial and mesenchymal cell tumors is one of the most common types of ovarian collision tumor.The O-RADS score of ovarian collision tumor is mostly≥4,which can sensitively detect malignant tumors.

Extended Deep Learning Algorithm for Improved Brain Tumor Diagnosis System

At present,the prediction of brain tumors is performed using Machine Learning(ML)and Deep Learning(DL)algorithms.Although various ML and DL algorithms are adapted to predict brain tumors to some range,some concerns still need enhancement,particularly accuracy,sensitivity,false positive and false negative,to improve the brain tumor prediction system symmetrically.Therefore,this work proposed an Extended Deep Learning Algorithm(EDLA)to measure performance parameters such as accuracy,sensitivity,and false positive and false negative rates.In addition,these iterated measures were analyzed by comparing the EDLA method with the Convolutional Neural Network(CNN)way further using the SPSS tool,and respective graphical illustrations were shown.The results were that the mean performance measures for the proposed EDLA algorithm were calculated,and those measured were accuracy(97.665%),sensitivity(97.939%),false positive(3.012%),and false negative(3.182%)for ten iterations.Whereas in the case of the CNN,the algorithm means accuracy gained was 94.287%,mean sensitivity 95.612%,mean false positive 5.328%,and mean false negative 4.756%.These results show that the proposed EDLA method has outperformed existing algorithms,including CNN,and ensures symmetrically improved parameters.Thus EDLA algorithm introduces novelty concerning its performance and particular activation function.This proposed method will be utilized effectively in brain tumor detection in a precise and accurate manner.This algorithm would apply to brain tumor diagnosis and be involved in various medical diagnoses aftermodification.If the quantity of dataset records is enormous,then themethod’s computation power has to be updated.

DCS, a novel classifier system based on disulfidptosis reveals tumor microenvironment heterogeneity and guides frontline therapy for clear cell renal carcinoma

Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown. Methods: In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified. Results: We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy. Conclusion: This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Intricate roles of estrogen and estrogen receptors in digestive system cancers:a systematic review

Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Blastomas of the digestive system in adults:A review

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor:A systematic review and metaanalysis

BACKGROUND Imatinib(IMA)has received approval as the primary treatment for gastrointestinal stromal tumors(GIST).Nonetheless,approximately half of the patients with advanced GIST show disease advancement following IMA treatment.Presently,the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted.Consequently,there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST.Ripretinib(RPT)is a new,switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action.AIM To investigate the literature on RPT to assess an effective,safe,and successful treatment strategy against advanced GIST.METHODS The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PubMed,Embase,Cochrane,Web of Science and ClinicalTrials.gov databases were screened from January 1,2003 to May 1,2024.RESULTS A total of 4 studies were included,with a total of 507 patients enrolled.The objective response rate(ORR)of the RPT-treated advanced GIST was 17%(95%CI:0.11-0.27),while the disease control rate(DCR)was 66%(95%CI:0.59-0.73).The overall occurrence of adverse events with varying degrees was 97%(95%CI:0.93-1),whereas that of grade≥3 adverse reactions was 42%(95%CI:0.28-0.63).The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR,DCR,and the occurrence of adverse events of grade 3 or higher.The publication bias was absent because no significant asymmetry was observed in Begg’s funnel plot in all studies.CONCLUSION RPT has favorable efficacy profiles in GIST patients,but the adverse reactions are obvious,and patient management needs to be strengthened to achieve better safety and tolerability.