BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 ...BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.展开更多
BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abd...BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity,the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors.CASE SUMMARY The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days.Upon physical examination,the patient had flat and tough abdomen with mild pressing pain at lower abdomen,no obvious abdominal mass was touchable,and shifting dullness was positive.Positron emission tomography-computed tomography(CT)showed that in his peritoneal cavity,there were multiple nodules of various sizes,seroperitoneum,multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules.Plain CT scanning at epigastrium/hypogastrium/pelvic cavity+enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity,peritoneum and right groin.Tumor marker of carbohydrate antigen 125 was 808 U/mL,diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia,and postoperative pathological examination confirmed EGIST.Imatinib was administered with better therapeutic effect.CONCLUSION Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation,and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.展开更多
Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a ...Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.展开更多
With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors...With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.展开更多
Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer...Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.展开更多
BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which...BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.展开更多
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 per...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.展开更多
BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making i...BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.展开更多
Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the...Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.展开更多
Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor rese...Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.展开更多
Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a...Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.展开更多
BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by exter...BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by external tumors of the scrotum is rare.The patient had both a greater omentum tumor and an inguinal hernia,and the tumor protruded into the scrotum through the hernia sac,which is even rarer.Moreover,omental tumors are mostly metastatic,and primary omental fibroma is rare.CASE SUMMARY Here,we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months.Preoperative examination and multidisciplinary discu-ssions considered intra-abdominal tumor displacement and inguinal hernia,and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum.Therefore,tumor resection and tension-free inguinal hernia repair were performed.The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia.CONCLUSION This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking,physical examination,and imaging before surgery.展开更多
In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarc...In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.展开更多
BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-...BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.展开更多
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca...Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.展开更多
BACKGROUND Solitary fibrous tumor(SFT)is a remarkably uncommon mesenchymal tumor.STAT6 level and a combination of clinical,pathological,and molecular features are required to arrive at a proper diagnosis.CASE SUMMARY ...BACKGROUND Solitary fibrous tumor(SFT)is a remarkably uncommon mesenchymal tumor.STAT6 level and a combination of clinical,pathological,and molecular features are required to arrive at a proper diagnosis.CASE SUMMARY In this report,we present an intriguing case involving a 43-year-old woman who initially exhibited symptoms of a bleeding retroperitoneal tumor,initially resembling a gastrointestinal stromal tumor,but later confirmed as an SFT.However,a year later,what was initially believed to be a recurrence of her SFT was instead identified as a desmoid tumor.CONCLUSION Distinguishing SFT from other tumors was pivotal.Correcting misdiagnoses of tumor type initially and of recurrence later was necessary for appropriate treatment of the correct desmoid type.展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptoma...Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia.Brown tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical practice.The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass.Furthermore,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion.The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and PTH.Although when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic tumors.Treatment of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical intervention.However,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.展开更多
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 ...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.展开更多
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.
文摘BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity,the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors.CASE SUMMARY The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days.Upon physical examination,the patient had flat and tough abdomen with mild pressing pain at lower abdomen,no obvious abdominal mass was touchable,and shifting dullness was positive.Positron emission tomography-computed tomography(CT)showed that in his peritoneal cavity,there were multiple nodules of various sizes,seroperitoneum,multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules.Plain CT scanning at epigastrium/hypogastrium/pelvic cavity+enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity,peritoneum and right groin.Tumor marker of carbohydrate antigen 125 was 808 U/mL,diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia,and postoperative pathological examination confirmed EGIST.Imatinib was administered with better therapeutic effect.CONCLUSION Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation,and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.
基金supported by the National Natural Science Foundation of China (No. 82203056)Natural Science Foundation of Liaoning Province (No. 2023-BS-167)+1 种基金Science and Technology Talent Innovation Support Plan of Dalian (No. 2022RQ091)“1+X” program for Clinical Competency Enhancement–Clinical Research Incubation Project of the Second Hospital of Dalian Medical University (No. 2022LCYJYB01)。
文摘Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.
文摘With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.
基金National Natural Science Foundation of China,No.82160842Clinical Research Project of Research Fund of Gansu Provincial Hospital,No.23GSSYD-17General Program of the Joint Scientific Research Fund,No.23JRRA1521.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.
基金supported by medical science research joint construction project of Henan(71188)Henan Provincial Department of Education under grant no.21B320008.
文摘Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.
基金Supported by National Natural Science Foundation of China,No.82074450Education Department of Hunan Province,No.21A0243,No.21B0374,No.22B0397,and No.22B0392+2 种基金Research Project of"Academician Liu Liang Workstation"of Hunan University of Traditional Chinese Medicine,No.21YS003Hunan Administration of Traditional Chinese Medicine,No.B2023001 and No.B2023009Hunan Provincial Natural Science Foundation of China,No.2023JJ40481。
文摘BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.
文摘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.
基金National Key R&D Program of China,No.2022YFF1203300.
文摘BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.
基金Supported by Nantong Municipal Health Commission,No.MSZ2022036.
文摘Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.
基金supported by the National Natural Science Foundation of China(No.82003298)the Scientiffc and Technological Project of Henan Province(No.232102310392)+5 种基金the Key Research and Development Projects of Henan Province(No.222102310453,212102311025)Postdoctoral Research Grant in Henan Province(No.201901025)the Key Research Project of Henan Higher Education Institutions(No.18A350003)Open Fund of Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Henan Province(No.NMZL2020102)the Natural Science Foundation of Chongqing(No.cstc2019jcyj-msxmX0035)the Scientiffc Research Seedling Project of Chongqing Medicinal Biotechnology Association(No.cmba2022kyym-zkxmQ0009).
文摘Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
基金This work was supported by the Basic Research Program of Yunnan Province-Joint Project of Kunming Medical University No.202101AY070001−169.
文摘Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.
文摘BACKGROUND The most common causes of scrotal enlargement in patients include primary tumor of the scrotum,inflammation,hydrocele of the tunica vaginalis,and indirect inguinal hernia;scrotal enlargement caused by external tumors of the scrotum is rare.The patient had both a greater omentum tumor and an inguinal hernia,and the tumor protruded into the scrotum through the hernia sac,which is even rarer.Moreover,omental tumors are mostly metastatic,and primary omental fibroma is rare.CASE SUMMARY Here,we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months.Preoperative examination and multidisciplinary discu-ssions considered intra-abdominal tumor displacement and inguinal hernia,and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum.Therefore,tumor resection and tension-free inguinal hernia repair were performed.The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia.CONCLUSION This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking,physical examination,and imaging before surgery.
文摘In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
基金reviewed and approved by the Hospital Pablo Tobón Uribe Institutional Review Board(Approval No.PG-DMD-046-F1).
文摘BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.
基金was supported by National Natural Science Foundation of China(81972893,82172719)Natural Science Foundation of Henan(212300410071)Training program for young key teachers in Henan Province(2020GGJS019).
文摘Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
文摘BACKGROUND Solitary fibrous tumor(SFT)is a remarkably uncommon mesenchymal tumor.STAT6 level and a combination of clinical,pathological,and molecular features are required to arrive at a proper diagnosis.CASE SUMMARY In this report,we present an intriguing case involving a 43-year-old woman who initially exhibited symptoms of a bleeding retroperitoneal tumor,initially resembling a gastrointestinal stromal tumor,but later confirmed as an SFT.However,a year later,what was initially believed to be a recurrence of her SFT was instead identified as a desmoid tumor.CONCLUSION Distinguishing SFT from other tumors was pivotal.Correcting misdiagnoses of tumor type initially and of recurrence later was necessary for appropriate treatment of the correct desmoid type.
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
文摘Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia.Brown tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical practice.The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass.Furthermore,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion.The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and PTH.Although when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic tumors.Treatment of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical intervention.However,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.
基金Supported by Hunan Provincial Natural Science Foundation Regional Joint Fund,No.2023JJ50050.
文摘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.