BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammatio...BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammation.It affects patients’survival,functional status,and quality of life profoundly.Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia.The gut microbiota,through its intricate interplay with iron metabolism,inflammatory pathways,and immune modulation,may either exacerbate or ameliorate anemia depending on its composition,and functional integrity.Dysbiosis,characterized by disruption in the gut microbial ecosystem,is very common in cancer patients.This microbial imbalance is implicated in anemia causation through diminished iron absorption,persistent low-grade inflammation,and suppression of erythropoiesis.AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies.It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia,identifies unique challenges associated with various cancer types,and evaluates the efficacy of microbiome-focused therapies.Through this integrative approach,the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.METHODS A literature search was performed using multiple databases,including Google Scholar,PubMed,Scopus,and Web of Science,using a combination of keywords and Boolean operators to refine results.Keywords included“cancerassociated anemia”,“gut microbiome”,“intestinal microbiota”,“iron metabolism”,“gut dysbiosis”,“short-chain fatty acids”,“hematopoiesis”,“probiotics”,“prebiotics”,and“fecal microbiota transplantation”.Articles published in English between 2000 and December 2024 were included,with a focus on contemporary and relevant findings.RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis,such as probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation(FMT),can inhibit anemia-causing pathways by enhancing microbial diversity,suppressing detrimental flora,reducing systemic inflammation and optimizing nutrient absorption.CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients.Microbiome-centered interventions,such as probiotics,prebiotics,dietary modifications,and FMT,have shown efficacy in restoring microbial balance,reducing inflammation,and enhancing nutrient bioavailability.Emerging approaches,including engineered probiotics and bacteriophage therapies,are promising precision-based,customizable solutions for various microbiome compositions and imbalances.Future research should focus on integrating microbiometargeted strategies with established anemia therapies.展开更多
The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty ...The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.展开更多
The resistance to cancer treatment is a major clinical obstacle,being strongly influenced by the tumor microen-vironment(TME).Cancer-associated fibroblasts(CAFs)are critical elements of the TME.CAFs are heterogeneous ...The resistance to cancer treatment is a major clinical obstacle,being strongly influenced by the tumor microen-vironment(TME).Cancer-associated fibroblasts(CAFs)are critical elements of the TME.CAFs are heterogeneous and are activated through diverse pathways.These CAFs engage in reciprocal interactions with tumor cells,driv-ing tumor progression and therapeutic resistance.In this review,we discuss the role of CAFs in the development of tumor resistance to chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Besides,we sum-marize recent clinical trials in CAF-targeted therapies.The development of resistance involves physical barrier formation,metabolic reprogramming,exosome release,DNA repair,bypass pathway activation,multidrug resis-tance protein upregulation,and immune checkpoint inhibition.Challenges remain in addressing drug resistance despite the therapeutic potential of targeting CAFs:the cellular origins of CAFs need to be clarified,and their limited clinical applications need to be increased.Future studies should focus on elucidating the reasons for CAF heterogeneity,developing precise targeting strategies,and validating the clinical safety and efficacy of CAF-based therapies to overcome treatment resistance and improve patient outcomes.展开更多
Colorectal cancer(CRC),the third most prevalent cancer globally,exhibits a notable association with venous thromboembolism(VTE),significantly impacting patient morbidity and mortality.We delve into the complex pathoge...Colorectal cancer(CRC),the third most prevalent cancer globally,exhibits a notable association with venous thromboembolism(VTE),significantly impacting patient morbidity and mortality.We delve into the complex pathogenesis of cancer-associated thrombosis(CAT)in CRC,highlighting the interplay of clinical risk factors and tumor-specific mechanisms.Our comprehensive review synthesizes the current understanding of CRC’s pro-thrombotic tendencies,examining both general clinical factors(e.g.,age,gender,obesity,prior VTE history)and tumor-specific aspects(e.g.,tumor location,stage,targeted therapies).Key findings illustrate how CRC cells themselves actively contribute to coagulation cascade activation through various procoagulant elements such as tissue factor,cancer procoagulant,and extracellular vesicles.We also explore how CRC influences host cells to adopt a procoagulant phenotype,thereby exacerbating thrombotic risks.This review underscores the role of genetic mutations in CRC(e.g.,KRAS,p53)in modulating coagulation-related protein expression and thrombosis risks.An in-depth understanding of the genetic landscape specific to CRC subtypes is essential for developing targeted anticoagulation strategies and could significantly advance thrombosis prevention while improving the overall management of patients with CRC.This highlights the urgent need for precision in addressing CAT within clinical settings.展开更多
Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous ...Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous system,and we have focused on cancer-associated fibroblasts(CAFs)for decades,it’s imperative to elucidate the impact of CAFs on SCs in PNI+OSCCs.We describe a disease progression-driven shift of PNI−towards PNI+during the progression of early-stage OSCC(31%,n=125)to late-stage OSCC(53%,n=97),characterized by abundant CAFs and nerve demyelination.CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro,and this involved up-regulated ER stress and decreased MAPK signals.Moreover,CAFs also aggravated the paralysis of the hind limb and PNI in vivo.Unexpectedly,leukemia inhibitory factor(LIF)was exclusively expressed on CAFs and up-regulated in metastatic OSCC.The LIF inhibitor EC330 restored CAF-induced SC inactivation.Thus,OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.展开更多
Osteosarcoma(OS)is a prevalent primary bone malignancy with limited treatment options.Therefore,it is imperative to investigate and understand the mechanisms underlying OS pathogenesis.Cancer-associated fibroblasts(CA...Osteosarcoma(OS)is a prevalent primary bone malignancy with limited treatment options.Therefore,it is imperative to investigate and understand the mechanisms underlying OS pathogenesis.Cancer-associated fibroblasts(CAFs)are markedly abundant in tumor stromal cells and are essentially involved in the modulation of tumor occurrence and development.In recent years,CAFs have become a hotspot as researchers aim to elucidate CAF mechanisms that regulate tumor progression.However,most studies on CAFs are limited to a few common cancers,and their association with OS remains elusive.This review describes the role and current knowledge of CAFs in OS,focusing on their potential cellular origin,classification,and diverse functionality.It was found that CAFs influenced OS tumor cell signaling,proliferation,invasion,metastasis,epithelial-mesenchymal transition,stemness maintenance,angiogenesis,and the ability to modify immune system components.Furthermore,findings on other common cancers indicated that effective therapeutic strategies included the manipulation of CAF activation,targeting CAF-derived components,and depletion of CAFs by biomarkers.This review provides new insights and a theoretical basis for OS research.展开更多
Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is ...Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.展开更多
Within the intricate milieu of colorectal cancer(CRC)tissues,cancer-associated fibroblasts(CAFs)act as pivotal orchestrators,wielding considerable influence over tumor progression.This review endeavors to dissect the ...Within the intricate milieu of colorectal cancer(CRC)tissues,cancer-associated fibroblasts(CAFs)act as pivotal orchestrators,wielding considerable influence over tumor progression.This review endeavors to dissect the multifaceted functions of CAFs within the realm of CRC,thereby highlighting their indispensability in fostering CRC malignant microenvironment and indicating the development of CAFs-targeted therapeutic interventions.Through a comprehensive synthesis of current knowledge,this review delineates insights into CAFsmediated modulation of cancer cell proliferation,invasiveness,immune evasion,and neovascularization,elucidating the intricate web of interactions that sustain the pro-tumor metabolism and secretion of multiple factors.Additionally,recognizing the high level of heterogeneity within CAFs is crucial,as they encompass a range of subtypes,including myofibroblastic CAFs,inflammatory CAFs,antigen-presenting CAFs,and vessel-associated CAFs.Innovatively,the symbiotic relationship between CAFs and the intestinal microbiota is explored,shedding light on a novel dimension of CRC pathogenesis.Despite remarkable progress,the orchestrated dynamic functions of CAFs remain incompletely deciphered,underscoring the need for continued research endeavors for therapeutic advancements in CRC management.展开更多
Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associ...Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.展开更多
Cachexia represents a chronic,multiorgan,integrative wasting disease.Patients with advanced cancer often develop cachexia,denoted as"cancer-associated cachexia".Cancer-associated cachexia remains a formidabl...Cachexia represents a chronic,multiorgan,integrative wasting disease.Patients with advanced cancer often develop cachexia,denoted as"cancer-associated cachexia".Cancer-associated cachexia remains a formidable challenge that plagues mankind,prompting ongoing efforts in both Western and Chinese medicine to find viable solutions;however,as of yet,no effective treatment that can reverse cancer-associated cachexia has been identified.Integrating Chinese and Western medicine approaches has shown promise in mitigating the symptoms of wasting and anorexia associated with cancer-associated cachexia,potentially heralding a novel paradigm in its treatment and management.In this article,we summarize existing mechanistic studies and treatment modalities through a comprehensive review of relevant literature and research findings,elucidating potential challenges and future avenues for development in the treatment of"cancer-associated cachexia"using an integrated Chinese and Western medicine approach.展开更多
AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gas...AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside Ⅳ.CONCLUSION Astragaloside Ⅳ can inhibit the pathological functions of GCAFs by correcting their dysregulation of micro RNA expression,and it is promisingly a potent therapeutic agent regulating tumor microenvironment.展开更多
Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of ...Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.展开更多
Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a...Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition,angiogenesis,metabolism reprogramming and chemoresistance.However,the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown.Micro RNAs(mi RNAs) are a class of non-coding small RNA molecules,and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs.In this review,we provide an overview of recent studies on CAF mi RNAs in GC and the relevant signaling pathways in gastrointestinal tumors.Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies.展开更多
The significant influence of tumor stroma on malignant cells has been extensively investigated in this era of targeted therapy. The tumor microenvironment, as a dynamic system, is orchestrated by various cells includi...The significant influence of tumor stroma on malignant cells has been extensively investigated in this era of targeted therapy. The tumor microenvironment, as a dynamic system, is orchestrated by various cells including tumor vascular composing cells, inflammatory cells and fibroblasts. As a major and important component in tumor stroma, increasing evidence has shown that spindle-shaped cancer-associated fibroblasts (CAFs) are a significant modifier of cancer evolution, and promote tumorigenesis, tumor invasion and metastasis by stimulating angiogenesis, malignant cell survival, epithelial-mesenchymal transition (EMT) and proliferation via direct cell-to-cell contact or secretion of soluble factors in most digestive solid tumors. CAFs are thought to be activated, characterized by the expression of α-smooth muscle actin, fibroblast activated protein, fibroblast specific protein, vimentin, fibronectin, etc. They are hypothesized to originate from normal or aged fibroblasts, bone marrow-derived mesenchymal cells, or vascular endothelial cells. EMT may also be an important process generating CAFs, and most probably, CAFs may originate from multiple cells. A close link exists between EMT, tumor stem cells, and chemo-resistance of tumor cells, which is largely orchestrated by CAFs. CAFs significantly induce immunosuppression, and may be a prognostic marker in various malignancies. Targeted therapy toward CAFs has displayed promising anticancer efficacy, which further reinforces the necessity to explore the relationship between CAFs and their hosts.展开更多
AIM To clone novel gastric cancer-associated genes and investigate their roles in gastric cancer occurrence.METHODS A method called differential display was used which allows the identification of differentially expre...AIM To clone novel gastric cancer-associated genes and investigate their roles in gastric cancer occurrence.METHODS A method called differential display was used which allows the identification of differentially expressed genes by using PAGE to display PCR-amplified cDNA fragments between gastric cancer cells and normal gastric mucosa cells. These fragments were cloned into plasmid vector pUC18. Homology analysis was made after sequencing these fragments.RESULTS Two novel genes were identified compared with sequences from GenBank. One was registered with the AD number AF 051783. In situ hybridization showed that these two novel genes expressed specifically in gastric cancer tissues.CONCLUSION The two novel genes obtained by differential display were confirmed to be gastric cancer-associated genes using in situ hybridization.展开更多
Objective： Cancer-associated fibroblasts （CAFs） are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than...Objective： Cancer-associated fibroblasts （CAFs） are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods： Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was con- ducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS） ProteinChip platform. Results： Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of a-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio （m/z） 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin 13-4-like protein 3, and tight junction-associated protein 1. Conclusions： Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.展开更多
Cancer-associated retinopathy (CAR) typically has a sudden or progressive onset of severe visual loss and an ominous association with an occult malignancy which contains breast cancer. Pathologically, CAR is the degen...Cancer-associated retinopathy (CAR) typically has a sudden or progressive onset of severe visual loss and an ominous association with an occult malignancy which contains breast cancer. Pathologically, CAR is the degeneration of photoreceptors. But the precise mechanism has not been fully established, CAR may result from autoimmune mediated apoptosis. And in recent years, there also have been some results demonstrating that tumor derived angiogenic factors such as VEGF may also confer the development of CAR, which may offer novel avenues for the therapeutic intervention in CAR. Early initiation of immunosuppressive therapy is critical for vision preservation. Future developments in rapid identification and longitudinal quantification of antibody levels would enable individualized management in these patients. The goal of this review was to analyze the epidemiology, the clinical features, the diagnosis and management of retinopathy in the context of recent advances in the elucidation of breast cancer-associated retinopathy (BCAR) pathogenesis.展开更多
Monoclonal antibodies against colon and pancreatic cancer, CL-2, CL-3, PS-9, PS-10, were used to detect the associated antigens in feces of patients with gastrointestinal carcinoma and non-cancer diseases. Binding inh...Monoclonal antibodies against colon and pancreatic cancer, CL-2, CL-3, PS-9, PS-10, were used to detect the associated antigens in feces of patients with gastrointestinal carcinoma and non-cancer diseases. Binding inhibition test by SABC-ELISA method were performed for the measurement of the antigen level. Results showed that the associated antigen detected in feces of patients with colon cancer were significantly higher than that of non-cancer disease or normal subjects. The positive rates were 61.1% as detected with CL-2; 53.4% with CL-3; 55.0%, PS-9; and 53.3% PS-10 in cancer patients while that in normal subjects were 7%; 9%; 8%; and 8% respectively. When 'cocktail' of CL-2, PS-9 and PS-10 were used, the positive rates were 92.5% in colon cancer and 14% in normal subjects. In seven out of the sixty patients with colon cancer studied who were graded as Dukes A, the results were all positive. The results seem superior to the serologic detection and may provide a promising new approach in the early diagnosis of colon cancer.展开更多
Tumor microenvironment plays a very important role in the growth,invasion and metastasis of tumor cells.The tumor interstitial microenvironment is an important part of the tumor microenvironment,which includes two par...Tumor microenvironment plays a very important role in the growth,invasion and metastasis of tumor cells.The tumor interstitial microenvironment is an important part of the tumor microenvironment,which includes two parts:the non-cellular and cellular components of the tumor interstitium,specifically including the extracellular matrix,blood vessels,and interstitial cells.Among them,activated interstitial fibroblasts,namely cancer-associated fibroblasts(CAFs),are the main components of tumor interstitial cells,which are most closely related to tumor interstitial fibrosis and tumor progress,and are expected to become a new target for cancer treatment.展开更多
With the advancement of anticancer therapy,there is increasing interest in understanding the tumor microenvi-ronment(TME).Cancer-associated fibroblasts(CAFs)play a pivotal role in the TME and have been the focus of mu...With the advancement of anticancer therapy,there is increasing interest in understanding the tumor microenvi-ronment(TME).Cancer-associated fibroblasts(CAFs)play a pivotal role in the TME and have been the focus of much research in recent years.CAFs play an active role in cancer progression through complex interactions with other cells in the TME,releasing regulatory factors,synthesizing and remodeling the extracellular matrix.How-ever,research on the role of CAFs in renal cell carcinoma(RCC)is still in its nascent stages.Here,we describe the origins and subgroups of CAFs,the roles of CAFs in the development and progression of RCC,the impact of CAFs on RCC prognosis,and the potential of CAFs as treatment targets in RCC.By analyzing CAF subsets,biomarkers,and targeted therapies,we present the significance and contribution of CAFs in RCC research.Furthermore,we highlight the distinct contribution of CAFs in advanced RCC through horizontal comparison with other cancers.This paper provides a comprehensive perspective of recent and foundational studies on the role of CAFs in RCC and other types of cancers and new insights for further study of CAFs in RCC.展开更多
文摘BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies,which stems from the direct effects of malignancy,treatment-induced toxicities,and systemic inflammation.It affects patients’survival,functional status,and quality of life profoundly.Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia.The gut microbiota,through its intricate interplay with iron metabolism,inflammatory pathways,and immune modulation,may either exacerbate or ameliorate anemia depending on its composition,and functional integrity.Dysbiosis,characterized by disruption in the gut microbial ecosystem,is very common in cancer patients.This microbial imbalance is implicated in anemia causation through diminished iron absorption,persistent low-grade inflammation,and suppression of erythropoiesis.AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies.It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia,identifies unique challenges associated with various cancer types,and evaluates the efficacy of microbiome-focused therapies.Through this integrative approach,the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.METHODS A literature search was performed using multiple databases,including Google Scholar,PubMed,Scopus,and Web of Science,using a combination of keywords and Boolean operators to refine results.Keywords included“cancerassociated anemia”,“gut microbiome”,“intestinal microbiota”,“iron metabolism”,“gut dysbiosis”,“short-chain fatty acids”,“hematopoiesis”,“probiotics”,“prebiotics”,and“fecal microbiota transplantation”.Articles published in English between 2000 and December 2024 were included,with a focus on contemporary and relevant findings.RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis,such as probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation(FMT),can inhibit anemia-causing pathways by enhancing microbial diversity,suppressing detrimental flora,reducing systemic inflammation and optimizing nutrient absorption.CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients.Microbiome-centered interventions,such as probiotics,prebiotics,dietary modifications,and FMT,have shown efficacy in restoring microbial balance,reducing inflammation,and enhancing nutrient bioavailability.Emerging approaches,including engineered probiotics and bacteriophage therapies,are promising precision-based,customizable solutions for various microbiome compositions and imbalances.Future research should focus on integrating microbiometargeted strategies with established anemia therapies.
文摘The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.
文摘The resistance to cancer treatment is a major clinical obstacle,being strongly influenced by the tumor microen-vironment(TME).Cancer-associated fibroblasts(CAFs)are critical elements of the TME.CAFs are heterogeneous and are activated through diverse pathways.These CAFs engage in reciprocal interactions with tumor cells,driv-ing tumor progression and therapeutic resistance.In this review,we discuss the role of CAFs in the development of tumor resistance to chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Besides,we sum-marize recent clinical trials in CAF-targeted therapies.The development of resistance involves physical barrier formation,metabolic reprogramming,exosome release,DNA repair,bypass pathway activation,multidrug resis-tance protein upregulation,and immune checkpoint inhibition.Challenges remain in addressing drug resistance despite the therapeutic potential of targeting CAFs:the cellular origins of CAFs need to be clarified,and their limited clinical applications need to be increased.Future studies should focus on elucidating the reasons for CAF heterogeneity,developing precise targeting strategies,and validating the clinical safety and efficacy of CAF-based therapies to overcome treatment resistance and improve patient outcomes.
文摘Colorectal cancer(CRC),the third most prevalent cancer globally,exhibits a notable association with venous thromboembolism(VTE),significantly impacting patient morbidity and mortality.We delve into the complex pathogenesis of cancer-associated thrombosis(CAT)in CRC,highlighting the interplay of clinical risk factors and tumor-specific mechanisms.Our comprehensive review synthesizes the current understanding of CRC’s pro-thrombotic tendencies,examining both general clinical factors(e.g.,age,gender,obesity,prior VTE history)and tumor-specific aspects(e.g.,tumor location,stage,targeted therapies).Key findings illustrate how CRC cells themselves actively contribute to coagulation cascade activation through various procoagulant elements such as tissue factor,cancer procoagulant,and extracellular vesicles.We also explore how CRC influences host cells to adopt a procoagulant phenotype,thereby exacerbating thrombotic risks.This review underscores the role of genetic mutations in CRC(e.g.,KRAS,p53)in modulating coagulation-related protein expression and thrombosis risks.An in-depth understanding of the genetic landscape specific to CRC subtypes is essential for developing targeted anticoagulation strategies and could significantly advance thrombosis prevention while improving the overall management of patients with CRC.This highlights the urgent need for precision in addressing CAT within clinical settings.
基金supported by the National Natural Science Foundation of China(82373037 and 82403486)the Natural Science Foundation of Jiangsu Province(BK20230054 and BK20230161)+1 种基金the China Postdoctoral Science Foundation(2023M741766)the Nanjing Medical Science and Technology Development Foundation,Nanjing Department of Health(YKK21182 and JQX23010).
文摘Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous system,and we have focused on cancer-associated fibroblasts(CAFs)for decades,it’s imperative to elucidate the impact of CAFs on SCs in PNI+OSCCs.We describe a disease progression-driven shift of PNI−towards PNI+during the progression of early-stage OSCC(31%,n=125)to late-stage OSCC(53%,n=97),characterized by abundant CAFs and nerve demyelination.CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro,and this involved up-regulated ER stress and decreased MAPK signals.Moreover,CAFs also aggravated the paralysis of the hind limb and PNI in vivo.Unexpectedly,leukemia inhibitory factor(LIF)was exclusively expressed on CAFs and up-regulated in metastatic OSCC.The LIF inhibitor EC330 restored CAF-induced SC inactivation.Thus,OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
基金supported by the National Natural Science Foundation of China(grant number 81773285)Beijing Chao-Yang Hospital Golden Seeds Foundation(grant number CYJZ202341).
文摘Osteosarcoma(OS)is a prevalent primary bone malignancy with limited treatment options.Therefore,it is imperative to investigate and understand the mechanisms underlying OS pathogenesis.Cancer-associated fibroblasts(CAFs)are markedly abundant in tumor stromal cells and are essentially involved in the modulation of tumor occurrence and development.In recent years,CAFs have become a hotspot as researchers aim to elucidate CAF mechanisms that regulate tumor progression.However,most studies on CAFs are limited to a few common cancers,and their association with OS remains elusive.This review describes the role and current knowledge of CAFs in OS,focusing on their potential cellular origin,classification,and diverse functionality.It was found that CAFs influenced OS tumor cell signaling,proliferation,invasion,metastasis,epithelial-mesenchymal transition,stemness maintenance,angiogenesis,and the ability to modify immune system components.Furthermore,findings on other common cancers indicated that effective therapeutic strategies included the manipulation of CAF activation,targeting CAF-derived components,and depletion of CAFs by biomarkers.This review provides new insights and a theoretical basis for OS research.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ80044)the Youth Science Foundation of Xiangya Hospital(2019Q13).
文摘Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.
文摘Within the intricate milieu of colorectal cancer(CRC)tissues,cancer-associated fibroblasts(CAFs)act as pivotal orchestrators,wielding considerable influence over tumor progression.This review endeavors to dissect the multifaceted functions of CAFs within the realm of CRC,thereby highlighting their indispensability in fostering CRC malignant microenvironment and indicating the development of CAFs-targeted therapeutic interventions.Through a comprehensive synthesis of current knowledge,this review delineates insights into CAFsmediated modulation of cancer cell proliferation,invasiveness,immune evasion,and neovascularization,elucidating the intricate web of interactions that sustain the pro-tumor metabolism and secretion of multiple factors.Additionally,recognizing the high level of heterogeneity within CAFs is crucial,as they encompass a range of subtypes,including myofibroblastic CAFs,inflammatory CAFs,antigen-presenting CAFs,and vessel-associated CAFs.Innovatively,the symbiotic relationship between CAFs and the intestinal microbiota is explored,shedding light on a novel dimension of CRC pathogenesis.Despite remarkable progress,the orchestrated dynamic functions of CAFs remain incompletely deciphered,underscoring the need for continued research endeavors for therapeutic advancements in CRC management.
基金Supported by the Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica(PAPIIT)de la Dirección General de Asuntos de Personal Académico,No.IN212722 and No.IA208424Consejo Mexiquense de Ciencia y Tecnología,No.CS000132Consejo Nacional de Humanidades,Ciencia y Tecnología,No.CF-2023-I-563.
文摘Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.
基金supported by China Center for the Development of Traditional Chinese Medicine Science and Technology Joint research project(CXZH202307)Shaanxi Province Traditional Chinese Medicine“Double Chain Integration”Young and Middle-aged Scientific Research and Innovation Team Project(2022-SLRH-LJ-006).
文摘Cachexia represents a chronic,multiorgan,integrative wasting disease.Patients with advanced cancer often develop cachexia,denoted as"cancer-associated cachexia".Cancer-associated cachexia remains a formidable challenge that plagues mankind,prompting ongoing efforts in both Western and Chinese medicine to find viable solutions;however,as of yet,no effective treatment that can reverse cancer-associated cachexia has been identified.Integrating Chinese and Western medicine approaches has shown promise in mitigating the symptoms of wasting and anorexia associated with cancer-associated cachexia,potentially heralding a novel paradigm in its treatment and management.In this article,we summarize existing mechanistic studies and treatment modalities through a comprehensive review of relevant literature and research findings,elucidating potential challenges and future avenues for development in the treatment of"cancer-associated cachexia"using an integrated Chinese and Western medicine approach.
基金Supported by the National Natural Science Foundation of China,No.81760552the Program of the Inner Mongolia Natural Science Foundation,No.2016MS0824 and No.2015MS0896+1 种基金the Program of“Keji Baiwan Gongcheng”of Inner Mongolia Medical University,No.YKD2015KJBW008the Supporting Program for Outstanding Youth in Science and Technology of Inner Mongolia Autonomous Region,No.NJYT-17-B30
文摘AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside Ⅳ.CONCLUSION Astragaloside Ⅳ can inhibit the pathological functions of GCAFs by correcting their dysregulation of micro RNA expression,and it is promisingly a potent therapeutic agent regulating tumor microenvironment.
基金Supported by University of Southern DenmarkOdense University Hospital Research Fund
文摘Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.
文摘Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition,angiogenesis,metabolism reprogramming and chemoresistance.However,the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown.Micro RNAs(mi RNAs) are a class of non-coding small RNA molecules,and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs.In this review,we provide an overview of recent studies on CAF mi RNAs in GC and the relevant signaling pathways in gastrointestinal tumors.Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies.
文摘The significant influence of tumor stroma on malignant cells has been extensively investigated in this era of targeted therapy. The tumor microenvironment, as a dynamic system, is orchestrated by various cells including tumor vascular composing cells, inflammatory cells and fibroblasts. As a major and important component in tumor stroma, increasing evidence has shown that spindle-shaped cancer-associated fibroblasts (CAFs) are a significant modifier of cancer evolution, and promote tumorigenesis, tumor invasion and metastasis by stimulating angiogenesis, malignant cell survival, epithelial-mesenchymal transition (EMT) and proliferation via direct cell-to-cell contact or secretion of soluble factors in most digestive solid tumors. CAFs are thought to be activated, characterized by the expression of α-smooth muscle actin, fibroblast activated protein, fibroblast specific protein, vimentin, fibronectin, etc. They are hypothesized to originate from normal or aged fibroblasts, bone marrow-derived mesenchymal cells, or vascular endothelial cells. EMT may also be an important process generating CAFs, and most probably, CAFs may originate from multiple cells. A close link exists between EMT, tumor stem cells, and chemo-resistance of tumor cells, which is largely orchestrated by CAFs. CAFs significantly induce immunosuppression, and may be a prognostic marker in various malignancies. Targeted therapy toward CAFs has displayed promising anticancer efficacy, which further reinforces the necessity to explore the relationship between CAFs and their hosts.
文摘AIM To clone novel gastric cancer-associated genes and investigate their roles in gastric cancer occurrence.METHODS A method called differential display was used which allows the identification of differentially expressed genes by using PAGE to display PCR-amplified cDNA fragments between gastric cancer cells and normal gastric mucosa cells. These fragments were cloned into plasmid vector pUC18. Homology analysis was made after sequencing these fragments.RESULTS Two novel genes were identified compared with sequences from GenBank. One was registered with the AD number AF 051783. In situ hybridization showed that these two novel genes expressed specifically in gastric cancer tissues.CONCLUSION The two novel genes obtained by differential display were confirmed to be gastric cancer-associated genes using in situ hybridization.
基金supported by the National Natural Science Foundation of China (Nos. 81000892, 81071801, and 30801341)the Research Fund for the Doctoral Program of Higher Education of China (No. 200803351107)
文摘Objective： Cancer-associated fibroblasts （CAFs） are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods： Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was con- ducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS） ProteinChip platform. Results： Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of a-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio （m/z） 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin 13-4-like protein 3, and tight junction-associated protein 1. Conclusions： Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.
文摘Cancer-associated retinopathy (CAR) typically has a sudden or progressive onset of severe visual loss and an ominous association with an occult malignancy which contains breast cancer. Pathologically, CAR is the degeneration of photoreceptors. But the precise mechanism has not been fully established, CAR may result from autoimmune mediated apoptosis. And in recent years, there also have been some results demonstrating that tumor derived angiogenic factors such as VEGF may also confer the development of CAR, which may offer novel avenues for the therapeutic intervention in CAR. Early initiation of immunosuppressive therapy is critical for vision preservation. Future developments in rapid identification and longitudinal quantification of antibody levels would enable individualized management in these patients. The goal of this review was to analyze the epidemiology, the clinical features, the diagnosis and management of retinopathy in the context of recent advances in the elucidation of breast cancer-associated retinopathy (BCAR) pathogenesis.
文摘Monoclonal antibodies against colon and pancreatic cancer, CL-2, CL-3, PS-9, PS-10, were used to detect the associated antigens in feces of patients with gastrointestinal carcinoma and non-cancer diseases. Binding inhibition test by SABC-ELISA method were performed for the measurement of the antigen level. Results showed that the associated antigen detected in feces of patients with colon cancer were significantly higher than that of non-cancer disease or normal subjects. The positive rates were 61.1% as detected with CL-2; 53.4% with CL-3; 55.0%, PS-9; and 53.3% PS-10 in cancer patients while that in normal subjects were 7%; 9%; 8%; and 8% respectively. When 'cocktail' of CL-2, PS-9 and PS-10 were used, the positive rates were 92.5% in colon cancer and 14% in normal subjects. In seven out of the sixty patients with colon cancer studied who were graded as Dukes A, the results were all positive. The results seem superior to the serologic detection and may provide a promising new approach in the early diagnosis of colon cancer.
文摘Tumor microenvironment plays a very important role in the growth,invasion and metastasis of tumor cells.The tumor interstitial microenvironment is an important part of the tumor microenvironment,which includes two parts:the non-cellular and cellular components of the tumor interstitium,specifically including the extracellular matrix,blood vessels,and interstitial cells.Among them,activated interstitial fibroblasts,namely cancer-associated fibroblasts(CAFs),are the main components of tumor interstitial cells,which are most closely related to tumor interstitial fibrosis and tumor progress,and are expected to become a new target for cancer treatment.
基金supported by grants from the Natural Science Founda-tion of Shanghai(graft number:20ZR1413100)Beijing Xisike Clinical Oncology Research Foundation(graft number:Y-HR2020MS-0948)+1 种基金the Shanghai Anti-Cancer Association Eyas Project(graft numbers:SACA-CY21A06,SACA-CY21B01)Shanghai Municipal Health Bureau(graft number:2020CXJQ03).
文摘With the advancement of anticancer therapy,there is increasing interest in understanding the tumor microenvi-ronment(TME).Cancer-associated fibroblasts(CAFs)play a pivotal role in the TME and have been the focus of much research in recent years.CAFs play an active role in cancer progression through complex interactions with other cells in the TME,releasing regulatory factors,synthesizing and remodeling the extracellular matrix.How-ever,research on the role of CAFs in renal cell carcinoma(RCC)is still in its nascent stages.Here,we describe the origins and subgroups of CAFs,the roles of CAFs in the development and progression of RCC,the impact of CAFs on RCC prognosis,and the potential of CAFs as treatment targets in RCC.By analyzing CAF subsets,biomarkers,and targeted therapies,we present the significance and contribution of CAFs in RCC research.Furthermore,we highlight the distinct contribution of CAFs in advanced RCC through horizontal comparison with other cancers.This paper provides a comprehensive perspective of recent and foundational studies on the role of CAFs in RCC and other types of cancers and new insights for further study of CAFs in RCC.
