Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diag...Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dy...Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion(PNI),a clinical pathological feature of PDAC.The formation and function of PNI are dually regulated by molecular(e.g.,involving neurotrophins,cytokines,chemokines,and neurotransmitters),metabolic(e.g.,serine metabolism),and cellular mechanisms(e.g.,involving Schwann cells,stromal cells,T cells,and macrophages).Such integrated mechanisms of PNI not only support tumor development,growth,invasion,and metastasis but also mediate the formation of pain,all of which are closely related to poor disease prognosis in PDAC.This review details the modulation,signaling pathways,detection,and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.展开更多
CD4^＋ CD25^＋ regulatory T （Treg） cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes （TDLNs...CD4^＋ CD25^＋ regulatory T （Treg） cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes （TDLNs） has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor- and TDLN-infiltrating Treg cells remains unclear. Here we provide heterogeneity analysis of tumor infiltrating human CD4^＋ Treg cells and their matched adjacent tissues and TDLNs. We defined three different subpopulations of tumor- and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma （PDAC） and confirmed their functional heterogeneity. Helios^＋ CCR8^＋ Treg cells with potent suppressor function and limited IL-2 and IFN-7 secretion were identified in tumors and TDLNs. On the contrary, Helios^- CCR8^- Treg cells have impaired suppressive activity, and elevated expression of pro-inflammatory cytokines. More advanced grades of PDAC have predominantly Helios^＋ CCR8^＋ Treg cells and few Helios^- CCR8^- Treg cells both in tumors and TDLNs that suggests poor prognosis. These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.展开更多
BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the r...BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is a common cause of cancer-related death,and most patients are with advanced disease when diagnosed.At present,despite a variety of treatments have been devel-oped for PDAC,few e...Pancreatic ductal adenocarcinoma(PDAC)is a common cause of cancer-related death,and most patients are with advanced disease when diagnosed.At present,despite a variety of treatments have been devel-oped for PDAC,few effective treatment options are available;on the other hand,PDAC shows significant resistance to chemoradiotherapy,targeted therapy,and immunotherapy due to its heterogeneous genetic profile,molecular signaling pathways,and complex tumor immune microenvironment.Nevertheless,over the past decades,there have been many new advances in the key theory and understanding of the in-trinsic mechanisms and complexity of molecular biology and molecular immunology in pancreatic can-cer,based on which more and more diverse new means and reasonable combination strategies for PDAC treatment have been developed and preliminary breakthroughs have been made.With the continuous ex-ploration,from surgical local treatment to comprehensive medical management,the research-diagnosis-management system of pancreatic cancer is improving.This review focused on the variety of treatments for advanced PDAC,including traditional chemotherapy,targeted therapy,immunotherapy,microenviron-ment matrix regulation as well as the treatment targeting epigenetics,metabolism and cancer stem cells.We pointed out the current research bottlenecks and future exploration directions.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment.PDAC overcomes these restrictions by employing unconventional tactics for th...Pancreatic ductal adenocarcinoma(PDAC)is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment.PDAC overcomes these restrictions by employing unconventional tactics for the procurement and usage of fuel sources.The substantial reprogramming of PDAC cell metabolism is driven by oncogene-mediated cell-autonomous pathways.PDAC cells use glucose,glutamine,and lipids for energy and depend on autophagy and macropinocytosis for survival and growth.They also interact metabolically with non-cancerous cells,aiding tumor progression.Many clinical trials focusing on altered metabolism are ongoing.Understanding the metabolic regulation of PDAC cells will not only help to increase understanding of the mechanisms of disease progression but also provide insights for the development of new diagnostic and therapeutic approaches.展开更多
Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse panc...Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas,animal models can recapitulate human disease.Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia(mPanIN).Additional inactivation of p16,p53,or transforming growth factor-βsignaling,in the context of Kras activation,dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma(PDAC)with abundant stromal expansion and marked fibrosis(desmoplasia).The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment,which is superior to xenograft models,although there are some limitations and differences from human PDAC.By fully studying GEM models,we can understand the mechanisms of PDAC formation and progression more precisely,which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.展开更多
AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. Th...AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups:control and aminoguanidine treated. Tumor growth,survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase,copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally,vascularization was determined by Massons trichromic staining,and by VEGF and CD34 expression.RESULTS:Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells,intratumoral vascularization (trichromic stain) and the expression of Ki-67,Bax,eNOS,CD34,VEGF,catalase,CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION:The antitumoral action of aminoguanidine is associated with decreased cell proliferation,reduced angiogenesis,and reduced expression of antioxidant enzymes.展开更多
Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus fo...Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus for can-cer research,and to accelerate collaborations between institutions and investigators.In this edition,the following 8 valuable questions are presented.Question 94.The origin of tumors:time for a new paradigm?Question 95.How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?Question 96.Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?Question 97.What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?Question 98.Is high local concentration of metformin essential for its anti-cancer activity?Question 99.How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?Question 100.Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?Question 101.Is cell migration a selectable trait in the natural evolution of carcinoma?展开更多
This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts pr...This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.展开更多
Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagno...Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.展开更多
The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecu...The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive malignancy.Despite the development of multimodality treatments,including surgical resection,radiotherapy,and chemotherapy,the long-term prognosis of patient...Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive malignancy.Despite the development of multimodality treatments,including surgical resection,radiotherapy,and chemotherapy,the long-term prognosis of patients with PDAC remains poor.Recently,the introduction of neoadjuvant treatment(NAT)has made more patients amenable to surgery,increasing the possibility of R0 resection,treatment of occult micro-metastasis,and prolongation of overall survival.Imaging plays a vital role in tumor response evaluation after NAT.However,conventional imaging modalities such as multidetector computed tomography have limited roles in the assessment of tumor resectability after NAT for PDAC because of the similar appearance of tissue fibrosis and tumor infiltration.Perfusion computed tomography,using blood perfusion as a biomarker,provides added value in predicting the histopathologic response of PDAC to NAT by reflecting the changes in tumor matrix and fibrosis content.Other imaging technologies,including diffusion-weighted imaging of magnetic resonance imaging and positron emission tomography,can reveal the tumor response by monitoring the structural changes in tumor cells and functional metabolic changes in tumors after NAT.In addition,with the renewed interest in data acquisition and analysis,texture analysis and radiomics have shown potential for the early evaluation of the response to NAT,thus improving patient stratification to achieve accurate and intensive treatment.In this review,we briefly introduce the application and value of NAT in resectable and unresectable PDAC.We also summarize the role of imaging in evaluating the response to NAT for PDAC,as well as the advantages,limitations,and future development directions of current imaging techniques.展开更多
BACKGROUND As the most common cancer in women,breast cancer is the leading cause of death.Most patients are initially diagnosed as stage I-III.Among those without distant metastases,64%are local tumors and 27%are regi...BACKGROUND As the most common cancer in women,breast cancer is the leading cause of death.Most patients are initially diagnosed as stage I-III.Among those without distant metastases,64%are local tumors and 27%are regional tumors.Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy(NACT).It is worth noting that the status of tumor cell biomarkers is not consistently static.Endocrine-related estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(HER2)encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa,especially in luminal B subtype after NACT.In addition,determination of HER2 status currently mainly relies on immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH),but FISH is commonly used when the result of IHC is uncertain.HER2 is regarded as negative when the IHC result is 0/1+without the addition of FISH.To the best of our knowledge,this is the first report of a case harboring HER2 status transformation and IHC1+with positive amplification by FISH after NACT.CASE SUMMARY A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup.Biopsies of the right breast lesion and axillary lymph nodes were obtained.The results pointed to invasive ductal carcinoma with the IHC result for ER(80%),PR(60%),Ki-67(20%)and ambiguous expression of HER2(IHC 2+)with negative amplification by FISH(HER2/CEP17 ratio of 1.13).She underwent surgery after NACT.The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm×0.8 cm×0.5 cm and had spread to one of fifteen dissected lymph nodes.Retesting of the specimen showed that the tumor was positive for ER(2+,85%)and PR(2+,10%)but negative for HER2 by IHC(1+).Also Ki-67 had dropped to 2%.The patient was regularly monitored every 3 mo without evidence of recurrence.CONCLUSION Biomark展开更多
基金Supported by NIH R01 CA169702-01A1(to Zheng L)NIH K23 CA148964-01(to Zheng L)+6 种基金Johns Hopkins School of Medicine Clinical Scientist Award(to Zheng L)Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins(to Zheng L)The National Pancreas Foundation(to Zheng L)Lefkofsky Family Foundation(to Zheng L)the NCI SPORE in Gastrointestinal Cancers P50 CA062924(to Zheng L)Lustgarten Foundation(to Zheng L)the Sol Goldman Pancreatic Cancer Center grants(to Zheng L)
文摘Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.
文摘Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells.Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion(PNI),a clinical pathological feature of PDAC.The formation and function of PNI are dually regulated by molecular(e.g.,involving neurotrophins,cytokines,chemokines,and neurotransmitters),metabolic(e.g.,serine metabolism),and cellular mechanisms(e.g.,involving Schwann cells,stromal cells,T cells,and macrophages).Such integrated mechanisms of PNI not only support tumor development,growth,invasion,and metastasis but also mediate the formation of pain,all of which are closely related to poor disease prognosis in PDAC.This review details the modulation,signaling pathways,detection,and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.
基金Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0501Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2022QNXM074.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.
基金supported by National Basic Research Program of China(2014CB541803 and 2014CB541903)the National Science Foundation of China(31525008,81330072,31670911,31370863+1 种基金SMCST 14JC1406100)Shanghai Academic Research Leader(16XD1403800)
文摘CD4^＋ CD25^＋ regulatory T （Treg） cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity. Abundant Treg cell accumulation in tumors and tumor draining lymph nodes （TDLNs） has been reported to correlate with both poor and favorable prognosis in various cancers, which suggests that Tregs may have multiple effects on antitumor immunity. However, the heterogeneity of tumor- and TDLN-infiltrating Treg cells remains unclear. Here we provide heterogeneity analysis of tumor infiltrating human CD4^＋ Treg cells and their matched adjacent tissues and TDLNs. We defined three different subpopulations of tumor- and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma （PDAC） and confirmed their functional heterogeneity. Helios^＋ CCR8^＋ Treg cells with potent suppressor function and limited IL-2 and IFN-7 secretion were identified in tumors and TDLNs. On the contrary, Helios^- CCR8^- Treg cells have impaired suppressive activity, and elevated expression of pro-inflammatory cytokines. More advanced grades of PDAC have predominantly Helios^＋ CCR8^＋ Treg cells and few Helios^- CCR8^- Treg cells both in tumors and TDLNs that suggests poor prognosis. These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.
文摘BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.
基金supported by grants from the National Key R&D Program of China(2016YFC1303800)Jilin Provincial Key Labora-tory of Biological Therapy(20170622011JC)+1 种基金Jilin Provincial Science and Technology Department(20190303146SF)Jilin Province Finance Department(2018SCZWSZX-010).
文摘Pancreatic ductal adenocarcinoma(PDAC)is a common cause of cancer-related death,and most patients are with advanced disease when diagnosed.At present,despite a variety of treatments have been devel-oped for PDAC,few effective treatment options are available;on the other hand,PDAC shows significant resistance to chemoradiotherapy,targeted therapy,and immunotherapy due to its heterogeneous genetic profile,molecular signaling pathways,and complex tumor immune microenvironment.Nevertheless,over the past decades,there have been many new advances in the key theory and understanding of the in-trinsic mechanisms and complexity of molecular biology and molecular immunology in pancreatic can-cer,based on which more and more diverse new means and reasonable combination strategies for PDAC treatment have been developed and preliminary breakthroughs have been made.With the continuous ex-ploration,from surgical local treatment to comprehensive medical management,the research-diagnosis-management system of pancreatic cancer is improving.This review focused on the variety of treatments for advanced PDAC,including traditional chemotherapy,targeted therapy,immunotherapy,microenviron-ment matrix regulation as well as the treatment targeting epigenetics,metabolism and cancer stem cells.We pointed out the current research bottlenecks and future exploration directions.
基金financially supported by the National Science Fund for National Natural Science Foundation of China(No.82125026,82330081)Taishan Scholars Program of Shandong Province(No.Ts20190987)Major State Basic Research Development Program of Natural Science Foundation of Shandong Province in China(No.ZR2020ZD11).
文摘Pancreatic ductal adenocarcinoma(PDAC)is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment.PDAC overcomes these restrictions by employing unconventional tactics for the procurement and usage of fuel sources.The substantial reprogramming of PDAC cell metabolism is driven by oncogene-mediated cell-autonomous pathways.PDAC cells use glucose,glutamine,and lipids for energy and depend on autophagy and macropinocytosis for survival and growth.They also interact metabolically with non-cancerous cells,aiding tumor progression.Many clinical trials focusing on altered metabolism are ongoing.Understanding the metabolic regulation of PDAC cells will not only help to increase understanding of the mechanisms of disease progression but also provide insights for the development of new diagnostic and therapeutic approaches.
文摘Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas,animal models can recapitulate human disease.Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia(mPanIN).Additional inactivation of p16,p53,or transforming growth factor-βsignaling,in the context of Kras activation,dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma(PDAC)with abundant stromal expansion and marked fibrosis(desmoplasia).The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment,which is superior to xenograft models,although there are some limitations and differences from human PDAC.By fully studying GEM models,we can understand the mechanisms of PDAC formation and progression more precisely,which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.
基金Supported by Grants from University of Buenos Aires (B098 and B112)
文摘AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups:control and aminoguanidine treated. Tumor growth,survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase,copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally,vascularization was determined by Massons trichromic staining,and by VEGF and CD34 expression.RESULTS:Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells,intratumoral vascularization (trichromic stain) and the expression of Ki-67,Bax,eNOS,CD34,VEGF,catalase,CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION:The antitumoral action of aminoguanidine is associated with decreased cell proliferation,reduced angiogenesis,and reduced expression of antioxidant enzymes.
文摘Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus for can-cer research,and to accelerate collaborations between institutions and investigators.In this edition,the following 8 valuable questions are presented.Question 94.The origin of tumors:time for a new paradigm?Question 95.How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?Question 96.Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?Question 97.What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?Question 98.Is high local concentration of metformin essential for its anti-cancer activity?Question 99.How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?Question 100.Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?Question 101.Is cell migration a selectable trait in the natural evolution of carcinoma?
文摘This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.
文摘Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.
基金Lei Zheng is supported by NIH grant R01 CA169702,NIH grant R01 CA197296,The Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins,National Cancer Institute Specialized Programs of Research Excellence in Gastrointestinal Cancers grant F50 CA062924,Sidney Kimmel Comprehensive Cancer Center grant P30 CA006973.
文摘The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.
文摘Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive malignancy.Despite the development of multimodality treatments,including surgical resection,radiotherapy,and chemotherapy,the long-term prognosis of patients with PDAC remains poor.Recently,the introduction of neoadjuvant treatment(NAT)has made more patients amenable to surgery,increasing the possibility of R0 resection,treatment of occult micro-metastasis,and prolongation of overall survival.Imaging plays a vital role in tumor response evaluation after NAT.However,conventional imaging modalities such as multidetector computed tomography have limited roles in the assessment of tumor resectability after NAT for PDAC because of the similar appearance of tissue fibrosis and tumor infiltration.Perfusion computed tomography,using blood perfusion as a biomarker,provides added value in predicting the histopathologic response of PDAC to NAT by reflecting the changes in tumor matrix and fibrosis content.Other imaging technologies,including diffusion-weighted imaging of magnetic resonance imaging and positron emission tomography,can reveal the tumor response by monitoring the structural changes in tumor cells and functional metabolic changes in tumors after NAT.In addition,with the renewed interest in data acquisition and analysis,texture analysis and radiomics have shown potential for the early evaluation of the response to NAT,thus improving patient stratification to achieve accurate and intensive treatment.In this review,we briefly introduce the application and value of NAT in resectable and unresectable PDAC.We also summarize the role of imaging in evaluating the response to NAT for PDAC,as well as the advantages,limitations,and future development directions of current imaging techniques.
文摘BACKGROUND As the most common cancer in women,breast cancer is the leading cause of death.Most patients are initially diagnosed as stage I-III.Among those without distant metastases,64%are local tumors and 27%are regional tumors.Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy(NACT).It is worth noting that the status of tumor cell biomarkers is not consistently static.Endocrine-related estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(HER2)encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa,especially in luminal B subtype after NACT.In addition,determination of HER2 status currently mainly relies on immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH),but FISH is commonly used when the result of IHC is uncertain.HER2 is regarded as negative when the IHC result is 0/1+without the addition of FISH.To the best of our knowledge,this is the first report of a case harboring HER2 status transformation and IHC1+with positive amplification by FISH after NACT.CASE SUMMARY A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup.Biopsies of the right breast lesion and axillary lymph nodes were obtained.The results pointed to invasive ductal carcinoma with the IHC result for ER(80%),PR(60%),Ki-67(20%)and ambiguous expression of HER2(IHC 2+)with negative amplification by FISH(HER2/CEP17 ratio of 1.13).She underwent surgery after NACT.The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm×0.8 cm×0.5 cm and had spread to one of fifteen dissected lymph nodes.Retesting of the specimen showed that the tumor was positive for ER(2+,85%)and PR(2+,10%)but negative for HER2 by IHC(1+).Also Ki-67 had dropped to 2%.The patient was regularly monitored every 3 mo without evidence of recurrence.CONCLUSION Biomark
