BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late diagnosis.Understanding the correlation between pathological type and imaging features ...BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late diagnosis.Understanding the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment planning.AIM To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging features.METHODS We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2010 and December 2020 at our institution.Pathological types were determined by histopathological examination of the surgical spe-cimens or biopsy samples.The imaging features were assessed using computed tomography,magnetic resonance imaging,and endoscopic ultrasound.Statistical analyses were performed to identify significant associations between pathological types and specific imaging characteristics.RESULTS There were 320(64%)cases of pancreatic ductal adenocarcinoma,75(15%)of intraductal papillary mucinous neoplasms,50(10%)of neuroendocrine tumors,and 55(11%)of other rare types.Distinct imaging features were identified in each pathological type.Pancreatic ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography,whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural nodules.Neuroendocrine tumors often appear as hypervascular lesions in contrast-enhanced imaging.Statistical analysis revealed significant correlations between specific imaging features and pathological types(P<0.001).CONCLUSION This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging features.These findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.展开更多
Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outco...Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.展开更多
This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers t...This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term outcomes.These biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk index.The PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.展开更多
This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a...This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.展开更多
BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for surgery.PC is prone to rec...BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for surgery.PC is prone to recurrence and metastasis,and the antitumor effect of chemotherapy is notably limited.CASE SUMMARY Histopathological analysis of a 53-year-old female PC patient who underwent Whipple surgery revealed poorly differentiated tumor cells infiltrating nerves,lymphatics,and blood vessels.The patient received two different first-line chemotherapy regimens consecutively;however,both regimens struggled to control disease progression.During this period,the patient underwent liver metastasis ablation surgery,Candida albicans liver abscess,and stereotactic body radiotherapy.With the addition of camrelizumab to the modified FOLFIRINOX regimen,tumor control was achieved.The patient subsequently refused to continue chemotherapy,and the antitumor regimen was changed to a combination of camrelizumab and apatinib.After patients received a combination of immunotherapy and targeted therapy,the length of hospital stay was significantly reduced.Furthermore,all side effects were within acceptable limits,leading to an improved quality of life and prolonged progression-free survival.Unfortunately,the pain associated with cancer,coupled with the side effects of opioid analgesics,has led the patient to reject all available anticancer treatment options.Approximately one month after camrelizumab and apatinib were discontinued without medical authorization,the PC recurred and rapidly progressed to widespread metastasis,ultimately leading to the patient's death approximately one month later.The overall survival was 2 years.CONCLUSION Immunotherapy and targeted therapy have the potential to increase both the quality of life and survival time of PC patients,particularly those whose tumor progression is not effectively controlled by chemotherapy alone.Nevertheless,further clinical trials are necessary to validate these findings.展开更多
Objective:To explore symptom experiences and self-coping patterns during the early and late stages of chemotherapy in these patients to provide a basis for developing targeted symptom management strategies.Methods:A t...Objective:To explore symptom experiences and self-coping patterns during the early and late stages of chemotherapy in these patients to provide a basis for developing targeted symptom management strategies.Methods:A total of 27 patients with pancreatic cancer undergoing chemotherapy at two medical institutions were recruited between November 2023 and August 2024.Semi-structured interviews were conducted in person or over the phone.Data were analyzed using traditional content and thematic analyses.Results:Three themes were identified:symptom experience,self-coping patterns,and existing obstacles.During the early stages of chemotherapy,patients reported a higher frequency of unpleasant symptoms and recognized these symptoms earlier in the treatment course.Patients in the early stages primarily relied on external support to cope with symptoms,while those in the later stages adopted self-care strategies.Several challenges related to unpleasant symptoms were observed,which appeared to correlate with the self-coping patterns employed.Conclusion:Patients with pancreatic cancer undergoing chemotherapy experience a complex and diverse range of symptoms,with varying coping patterns at different stages of treatment.Symptom management during chemotherapy presents significant challenges.Healthcare providers should improve the ongoing monitoring of symptoms post-chemotherapy.By linking patients’symptom experiences and self-coping patterns at different stages of chemotherapy to their specific challenges,personalized symptom management strategies can be developed to enhance care quality.展开更多
BACKGROUND Pancreatic cancer(PC)is one of the most aggressive malignancies characterized by rapid progression and poor prognosis.The involvement of cancer stem cells(CSCs)and Octamer transcription factor 4(OCT4)in PC ...BACKGROUND Pancreatic cancer(PC)is one of the most aggressive malignancies characterized by rapid progression and poor prognosis.The involvement of cancer stem cells(CSCs)and Octamer transcription factor 4(OCT4)in PC pathobiology is being increasingly recognized.AIM To investigate the role of OCT4 in pancreatic CSCs and its effect on PC cell prolif-eration,migration,drug sensitivity,and stemness maintenance.METHODS We analyzed OCT4 and CD133 expression in PC tissues and cell lines.BxPC-3 cells were used to assess the effects of OCT4 modulation on cellular behavior.Proliferation,migration,and stemness of BxPC-3 cells were evaluated,and the PI3K/AKT/mTOR pathway was examined to gain mechanistic insights.RESULTS OCT4 and CD133 were significantly overexpressed in PC tissues.OCT4 mo-dulation altered BxPC-3 cell proliferation,invasion,and stemness,with OCT4 overexpression(OV-OCT4)enhancing these properties and OCT4 interference decreasing them.OV-OCT4 activated the PI3K/AKT/mTOR pathway,which correlated with an increase in PC stem cells(PCSC).CONCLUSION OCT4 plays a crucial role in PCSCs by influencing the aggressiveness and drug resistance of PC cells,thus presenting itself as a potential therapeutic target.展开更多
Objective:The role of intraoperative radiation therapy(IORT)in the management of resectable pancreatic cancer(RPC)remains unclear.To date,the application of IORT using a low-energy X-ray source has not been extensivel...Objective:The role of intraoperative radiation therapy(IORT)in the management of resectable pancreatic cancer(RPC)remains unclear.To date,the application of IORT using a low-energy X-ray source has not been extensively investigated.Therefore,this study was conducted to evaluate the safety and efficacy of IORT using a 50 kV X-ray source in treating RPC.Methods:Patients with RPC who underwent radical pancreatectomy and IORT were enrolled.The primary endpoint was time to treatment failure(TTF)survival,whereas the secondary endpoints were safety and overall survival(OS).Results:By November 2023,35 patients with RPC were treated according to the study protocol.The median TTF was 11.67 months,whereas the median OS for the cohort was 22.2 months.The local recurrence rate was 20%.The most common postoperative complication was pancreatic fistula.The incidence of delayed gastric emptying was 20%.Within 30 days after surgery,one patient experienced abdominal pain,another experienced vomiting,and one died because of abdominal infection and a grade C pancreatic fistula.Carcinoembryonic antigen(CEA)and D-dimer levels significantly correlated with TTF and OS in multivariate analyses.The carbohydrate antigen 19-9(CA19-9)level was another prognostic factor significantly associated with OS.Patients with low D-dimer and normal CA19-9 levels showed prolonged OS with an IORT dose≤15 Gy.Conclusions:This study supports use of IORT with a 50 kV X-ray source in treating RPC.IORT using a low-energy X-ray source was well-tolerated and feasible.Additionally,D-dimer,CEA,and CA19-9 levels may help identify patient profiles potentially benefitting from IORT.展开更多
BACKGROUND Survival rates of patients with advanced pancreatic cancer(APC)have been improved with palliative chemotherapy series.The current preferred first-line regimen consists of combination therapy of 5-fluorourac...BACKGROUND Survival rates of patients with advanced pancreatic cancer(APC)have been improved with palliative chemotherapy series.The current preferred first-line regimen consists of combination therapy of 5-fluorouracil(5-FU)/leucovorin(LV),irinotecan,and oxaliplatin(FOLFIRINOX)or gemcitabine plus albumin-bound paclitaxel(GNP).After failure of first-line chemotherapy,there are a few options for subsequent therapy including switch to the unused first-line regimen or nanoliposomal irinotecan and 5-FU/LV.However,there are limited studies on the efficacy of third-line chemotherapy after failure of second-line chemotherapy.AIM To identify patients with APC who might benefit from third-line chemotherapy.METHODS Medical records from a single tertiary hospital were retrospectively reviewed between 2012 and 2021.The study included patients with histologically or cytologically confirmed metastatic or locally APC who underwent first-line FOLFIRINOX or GNP and subsequently received third-line chemotherapy.Overall survival(OS)after diagnosis and OS after third-line chemotherapy(OS3)were defined as the interval from the diagnosis to all-cause death and the time between the initiation of the third-line chemotherapy to all-cause death,respectively.RESULTS A total of 141 patients were enrolled.The median patient age at diagnosis was 61.8 years(36.0-86.0),and 54.9%were male.The first-line regimen was FOLFIRINOX(67.4%)or GNP(32.6%).The second-line regimen was FOLFIRINOX(27.0%),GNP(52.5%),or other(20.6%).The median OS was 19.0 months,and the median OS3 and progression-free survival after third-line treatment were 15.3 and 7.3 weeks,respectively.With regard to the best tumor response during third-line chemotherapy,1.4%had partial response,24.8%had stable disease,and 59.6%had progressive disease.The following clinical factors before third-line chemotherapy affected OS3:Good performance status(PS),serum carbohydrate antigen 19-9(CA19-9)level<1000 U/mL,duration of second-line chemotherapy≥19 weeks,and no peritoneal seeding.CONCLUSION This study identified that patients with good PS,CA19-9<1000 U/mL,second-line chemotherapy≥19 weeks,and no peritoneal seeding before starting third-line treatment may benefit more from third-line chemotherapy.展开更多
Background: Pancreatic cancer is one of the most lethal malignancies, with postoperative recurrence severely affecting patient survival and prognosis. This study aims to develop and validate a clinical prediction mode...Background: Pancreatic cancer is one of the most lethal malignancies, with postoperative recurrence severely affecting patient survival and prognosis. This study aims to develop and validate a clinical prediction model for postoperative recurrence in pancreatic cancer patients, incorporating multiple preoperative, intraoperative, and postoperative factors to assist clinical decision-making. Methods: A retrospective study was conducted on 216 patients who underwent surgical treatment for pancreatic malignancy at the First Affiliated Hospital of Chongqing Medical University between January 2015 and January 2023. An independent external validation cohort of 76 patients from the Second Affiliated Hospital of Chongqing Medical University was used to validate the model. Seven independent risk factors for postoperative recurrence were identified through univariate and multivariate Cox regression analyses. The model’s performance was evaluated using the concordance index (C-index) and ROC curves, and its accuracy and clinical value were assessed using calibration curves and decision curve analysis (DCA). Results: The predictive model demonstrated good discriminatory power, with a C-index of 0.72 in the training cohort and 0.66 in the validation cohort. The ROC curves for predicting recurrence at 3, 6, and 12 months postoperatively showed AUC values ranging from 0.72 to 0.83, indicating strong predictive value. Calibration curves and DCA confirmed the model’s accuracy and clinical utility. Conclusion: This study successfully developed and validated a clinical prediction model that incorporates seven independent risk factors for postoperative recurrence in pancreatic cancer. The model provides a useful tool for predicting recurrence risk, aiding in the identification of high-risk patients, and informing clinical decision-making.展开更多
This letter to the editor critically appraises the study by Luo et al.While the study provides valuable insights into imaging-pathology correlations in pancreatic can-cer,we identify several opportunities for enhancin...This letter to the editor critically appraises the study by Luo et al.While the study provides valuable insights into imaging-pathology correlations in pancreatic can-cer,we identify several opportunities for enhancing its clinical relevance.Notably,the exclusion of magnetic resonance cholangiopancreatography and positron emission tomography/computed tomography imaging limits the study’s diag-nostic scope,as these modalities offer superior capabilities in differentiating benign from malignant lesions and assessing metabolic tumor activity.Addi-tionally,the retrospective,cross-sectional design restricts the potential for dyna-mic insights into disease progression.We also highlight the untapped potential of radiomics-based analyses,which could significantly improve diagnostic accuracy and prognostic assessments.We recommend integrating these advanced imaging modalities,adopting longitudinal study designs,and leveraging radiomics app-roaches in future research to enhance the diagnostic frameworks in pancreatic cancer imaging.展开更多
Pancreatic cancer is one of the solid tumors with the worst prognosis.Five-year survival rate is less than 10%.Surgical resection is the only potentially curative treatment,but the tumor is often diagnosed at an advan...Pancreatic cancer is one of the solid tumors with the worst prognosis.Five-year survival rate is less than 10%.Surgical resection is the only potentially curative treatment,but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients.Moreover,surgery is still associated with high post-operative morbidity,while other therapies still offer very disappointing results.This article reviews every aspect of pancreatic cancer,focusing on the elements that can improve prognosis.It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.展开更多
Pancreatic cancer(PanCa)is a catastrophic disease,being third lethal in both the genders around the globe.The possible reasons are extreme disease invasiveness,highly fibrotic and desmoplastic stroma,dearth of confirm...Pancreatic cancer(PanCa)is a catastrophic disease,being third lethal in both the genders around the globe.The possible reasons are extreme disease invasiveness,highly fibrotic and desmoplastic stroma,dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics.This inimitable tumor microenvironment(TME)or desmoplasia with excessive extracellular matrix accumulation,create an extremely hypovascular,hypoxic and nutrient-deficient zone inside the tumor.To survive,grow and proliferate in such tough TME,pancreatic tumor and stromal cells transform their metabolism.Transformed glucose,glu-tamine,fat,nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism,impart therapy resistance,and immunosuppression in PanCa.Thus,a finer knowledge of altered metabolism would uncover its metabolic susceptibilities.These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa.In this review,we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but i...BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.展开更多
BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,ofte...BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,often failing to capture the complexity of the disease.The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment.This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer.AIM To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules.METHODS This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2,PLAU,and CCNA2.The results were validated in an independent dataset.This study also examined the correlations between the model risk score and various clinical features,components of the immune microenvironment,chemotherapeutic drug sensitivity,and metabolism-related pathways.Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines.RESULTS The prognostic model demonstrated significant predictive value,with the risk score showing a strong correlation with clinical features:It was significantly associated with tumor grade(G)(bP<0.01),moderately associated with tumor stage(T)(aP<0.05),and significantly correlated with residual tumor(R)status(bP<0.01).There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs.Furthermore,the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer.CONCLUSION The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.展开更多
BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory...BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.展开更多
BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogen...BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.展开更多
BACKGROUND Systemic inflammation and nutrition play pivotal roles in cancer progression and can increase the risk of delayed recovery after surgical procedures.AIM To assess the significance of inflammatory and nutrit...BACKGROUND Systemic inflammation and nutrition play pivotal roles in cancer progression and can increase the risk of delayed recovery after surgical procedures.AIM To assess the significance of inflammatory and nutritional indicators for the prognosis and postoperative recovery of patients with pancreatic cancer(PC).METHODS Patients who were diagnosed with PC and underwent surgical resection at our hospital between January 1,2019,and July 31,2023,were enrolled in this retrospective observational cohort study.All the data were collected from the electronic medical record system.Seven biomarkers-the albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune–inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index(NRI),and geriatric NRI were assessed.RESULTS A total of 446 patients with PC met the inclusion criteria and were subsequently enrolled.Patients with early postoperative discharge tended to have higher PNI values and lower SII,NLR,and PLR values(all P<0.05).Through multivariable logistic regression analysis,the SII value emerged as an independent risk factor influencing early recovery after surgery.Additionally,both univariable and multivariable Cox regression analyses revealed that the PNI value was the strongest prognostic marker for overall survival(OS;P=0.028)and recurrence-free survival(RFS;P<0.001).The optimal cutoff PNI value was established at 47.30 using X-tile software.Patients in the PNI-high group had longer OS(P<0.001)and RFS(P=0.0028)times than those in the PNI-low group.CONCLUSION Preoperative systemic inflammatory-nutritional biomarkers may be capable of predicting short-term recovery after surgery as well as long-term patient outcomes.展开更多
The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial dispar...The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial disparities and risk factors.Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients.The study,which included 14.2 million admissions from 2016-2017,found that 2.6%of adult patients were diagnosed with CP,with white males being the majority.Multivariate regression analysis identified men,black individuals,those aged 40-59 years,and individuals with a body mass index(BMI)between 25 and 29.9 as having an increased risk for CP.Moreover,0.78%of CP patients also had PDAC,with older age and BMI being significant risk factors for developing PDAC in CP patients.The study also highlighted disparities in healthcare access and utilization among different socioeconomic and ethno-racial groups,which may impact the risk and outcomes of CP and PDAC.展开更多
文摘BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late diagnosis.Understanding the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment planning.AIM To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging features.METHODS We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2010 and December 2020 at our institution.Pathological types were determined by histopathological examination of the surgical spe-cimens or biopsy samples.The imaging features were assessed using computed tomography,magnetic resonance imaging,and endoscopic ultrasound.Statistical analyses were performed to identify significant associations between pathological types and specific imaging characteristics.RESULTS There were 320(64%)cases of pancreatic ductal adenocarcinoma,75(15%)of intraductal papillary mucinous neoplasms,50(10%)of neuroendocrine tumors,and 55(11%)of other rare types.Distinct imaging features were identified in each pathological type.Pancreatic ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography,whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural nodules.Neuroendocrine tumors often appear as hypervascular lesions in contrast-enhanced imaging.Statistical analysis revealed significant correlations between specific imaging features and pathological types(P<0.001).CONCLUSION This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging features.These findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.
文摘Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.
文摘This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term outcomes.These biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk index.The PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.
文摘This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.
文摘BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for surgery.PC is prone to recurrence and metastasis,and the antitumor effect of chemotherapy is notably limited.CASE SUMMARY Histopathological analysis of a 53-year-old female PC patient who underwent Whipple surgery revealed poorly differentiated tumor cells infiltrating nerves,lymphatics,and blood vessels.The patient received two different first-line chemotherapy regimens consecutively;however,both regimens struggled to control disease progression.During this period,the patient underwent liver metastasis ablation surgery,Candida albicans liver abscess,and stereotactic body radiotherapy.With the addition of camrelizumab to the modified FOLFIRINOX regimen,tumor control was achieved.The patient subsequently refused to continue chemotherapy,and the antitumor regimen was changed to a combination of camrelizumab and apatinib.After patients received a combination of immunotherapy and targeted therapy,the length of hospital stay was significantly reduced.Furthermore,all side effects were within acceptable limits,leading to an improved quality of life and prolonged progression-free survival.Unfortunately,the pain associated with cancer,coupled with the side effects of opioid analgesics,has led the patient to reject all available anticancer treatment options.Approximately one month after camrelizumab and apatinib were discontinued without medical authorization,the PC recurred and rapidly progressed to widespread metastasis,ultimately leading to the patient's death approximately one month later.The overall survival was 2 years.CONCLUSION Immunotherapy and targeted therapy have the potential to increase both the quality of life and survival time of PC patients,particularly those whose tumor progression is not effectively controlled by chemotherapy alone.Nevertheless,further clinical trials are necessary to validate these findings.
基金supported by the State Key Laboratory of Ultrasonic Medical Engineering/the Chongqing Science and Technology Bureau(Project No.2022KFKT7011)the Postdoctoral Fellowship Program of CPSF(GZC20233357)+1 种基金the Health Commission of Sichuan Province Medical Science and Technology Program(24QNMP007)the Medical Research Program of Health Commission of Chengdu(2023535).
文摘Objective:To explore symptom experiences and self-coping patterns during the early and late stages of chemotherapy in these patients to provide a basis for developing targeted symptom management strategies.Methods:A total of 27 patients with pancreatic cancer undergoing chemotherapy at two medical institutions were recruited between November 2023 and August 2024.Semi-structured interviews were conducted in person or over the phone.Data were analyzed using traditional content and thematic analyses.Results:Three themes were identified:symptom experience,self-coping patterns,and existing obstacles.During the early stages of chemotherapy,patients reported a higher frequency of unpleasant symptoms and recognized these symptoms earlier in the treatment course.Patients in the early stages primarily relied on external support to cope with symptoms,while those in the later stages adopted self-care strategies.Several challenges related to unpleasant symptoms were observed,which appeared to correlate with the self-coping patterns employed.Conclusion:Patients with pancreatic cancer undergoing chemotherapy experience a complex and diverse range of symptoms,with varying coping patterns at different stages of treatment.Symptom management during chemotherapy presents significant challenges.Healthcare providers should improve the ongoing monitoring of symptoms post-chemotherapy.By linking patients’symptom experiences and self-coping patterns at different stages of chemotherapy to their specific challenges,personalized symptom management strategies can be developed to enhance care quality.
基金Supported by Inner Mongolia Natural Science Foundation and the 3rd Affiliated of Inner Medical University,No.2021MS08067.
文摘BACKGROUND Pancreatic cancer(PC)is one of the most aggressive malignancies characterized by rapid progression and poor prognosis.The involvement of cancer stem cells(CSCs)and Octamer transcription factor 4(OCT4)in PC pathobiology is being increasingly recognized.AIM To investigate the role of OCT4 in pancreatic CSCs and its effect on PC cell prolif-eration,migration,drug sensitivity,and stemness maintenance.METHODS We analyzed OCT4 and CD133 expression in PC tissues and cell lines.BxPC-3 cells were used to assess the effects of OCT4 modulation on cellular behavior.Proliferation,migration,and stemness of BxPC-3 cells were evaluated,and the PI3K/AKT/mTOR pathway was examined to gain mechanistic insights.RESULTS OCT4 and CD133 were significantly overexpressed in PC tissues.OCT4 mo-dulation altered BxPC-3 cell proliferation,invasion,and stemness,with OCT4 overexpression(OV-OCT4)enhancing these properties and OCT4 interference decreasing them.OV-OCT4 activated the PI3K/AKT/mTOR pathway,which correlated with an increase in PC stem cells(PCSC).CONCLUSION OCT4 plays a crucial role in PCSCs by influencing the aggressiveness and drug resistance of PC cells,thus presenting itself as a potential therapeutic target.
基金supported by the Tianjin Science and Technology Commission key project(Grant No.21JCZDJC00980)Tianjin Science and Technology Commission project(Grant No.22ZXJBSY00030)Tianjin Health Research project(Grant No.TJWJ2022MS007)。
文摘Objective:The role of intraoperative radiation therapy(IORT)in the management of resectable pancreatic cancer(RPC)remains unclear.To date,the application of IORT using a low-energy X-ray source has not been extensively investigated.Therefore,this study was conducted to evaluate the safety and efficacy of IORT using a 50 kV X-ray source in treating RPC.Methods:Patients with RPC who underwent radical pancreatectomy and IORT were enrolled.The primary endpoint was time to treatment failure(TTF)survival,whereas the secondary endpoints were safety and overall survival(OS).Results:By November 2023,35 patients with RPC were treated according to the study protocol.The median TTF was 11.67 months,whereas the median OS for the cohort was 22.2 months.The local recurrence rate was 20%.The most common postoperative complication was pancreatic fistula.The incidence of delayed gastric emptying was 20%.Within 30 days after surgery,one patient experienced abdominal pain,another experienced vomiting,and one died because of abdominal infection and a grade C pancreatic fistula.Carcinoembryonic antigen(CEA)and D-dimer levels significantly correlated with TTF and OS in multivariate analyses.The carbohydrate antigen 19-9(CA19-9)level was another prognostic factor significantly associated with OS.Patients with low D-dimer and normal CA19-9 levels showed prolonged OS with an IORT dose≤15 Gy.Conclusions:This study supports use of IORT with a 50 kV X-ray source in treating RPC.IORT using a low-energy X-ray source was well-tolerated and feasible.Additionally,D-dimer,CEA,and CA19-9 levels may help identify patient profiles potentially benefitting from IORT.
文摘BACKGROUND Survival rates of patients with advanced pancreatic cancer(APC)have been improved with palliative chemotherapy series.The current preferred first-line regimen consists of combination therapy of 5-fluorouracil(5-FU)/leucovorin(LV),irinotecan,and oxaliplatin(FOLFIRINOX)or gemcitabine plus albumin-bound paclitaxel(GNP).After failure of first-line chemotherapy,there are a few options for subsequent therapy including switch to the unused first-line regimen or nanoliposomal irinotecan and 5-FU/LV.However,there are limited studies on the efficacy of third-line chemotherapy after failure of second-line chemotherapy.AIM To identify patients with APC who might benefit from third-line chemotherapy.METHODS Medical records from a single tertiary hospital were retrospectively reviewed between 2012 and 2021.The study included patients with histologically or cytologically confirmed metastatic or locally APC who underwent first-line FOLFIRINOX or GNP and subsequently received third-line chemotherapy.Overall survival(OS)after diagnosis and OS after third-line chemotherapy(OS3)were defined as the interval from the diagnosis to all-cause death and the time between the initiation of the third-line chemotherapy to all-cause death,respectively.RESULTS A total of 141 patients were enrolled.The median patient age at diagnosis was 61.8 years(36.0-86.0),and 54.9%were male.The first-line regimen was FOLFIRINOX(67.4%)or GNP(32.6%).The second-line regimen was FOLFIRINOX(27.0%),GNP(52.5%),or other(20.6%).The median OS was 19.0 months,and the median OS3 and progression-free survival after third-line treatment were 15.3 and 7.3 weeks,respectively.With regard to the best tumor response during third-line chemotherapy,1.4%had partial response,24.8%had stable disease,and 59.6%had progressive disease.The following clinical factors before third-line chemotherapy affected OS3:Good performance status(PS),serum carbohydrate antigen 19-9(CA19-9)level<1000 U/mL,duration of second-line chemotherapy≥19 weeks,and no peritoneal seeding.CONCLUSION This study identified that patients with good PS,CA19-9<1000 U/mL,second-line chemotherapy≥19 weeks,and no peritoneal seeding before starting third-line treatment may benefit more from third-line chemotherapy.
文摘Background: Pancreatic cancer is one of the most lethal malignancies, with postoperative recurrence severely affecting patient survival and prognosis. This study aims to develop and validate a clinical prediction model for postoperative recurrence in pancreatic cancer patients, incorporating multiple preoperative, intraoperative, and postoperative factors to assist clinical decision-making. Methods: A retrospective study was conducted on 216 patients who underwent surgical treatment for pancreatic malignancy at the First Affiliated Hospital of Chongqing Medical University between January 2015 and January 2023. An independent external validation cohort of 76 patients from the Second Affiliated Hospital of Chongqing Medical University was used to validate the model. Seven independent risk factors for postoperative recurrence were identified through univariate and multivariate Cox regression analyses. The model’s performance was evaluated using the concordance index (C-index) and ROC curves, and its accuracy and clinical value were assessed using calibration curves and decision curve analysis (DCA). Results: The predictive model demonstrated good discriminatory power, with a C-index of 0.72 in the training cohort and 0.66 in the validation cohort. The ROC curves for predicting recurrence at 3, 6, and 12 months postoperatively showed AUC values ranging from 0.72 to 0.83, indicating strong predictive value. Calibration curves and DCA confirmed the model’s accuracy and clinical utility. Conclusion: This study successfully developed and validated a clinical prediction model that incorporates seven independent risk factors for postoperative recurrence in pancreatic cancer. The model provides a useful tool for predicting recurrence risk, aiding in the identification of high-risk patients, and informing clinical decision-making.
文摘This letter to the editor critically appraises the study by Luo et al.While the study provides valuable insights into imaging-pathology correlations in pancreatic can-cer,we identify several opportunities for enhancing its clinical relevance.Notably,the exclusion of magnetic resonance cholangiopancreatography and positron emission tomography/computed tomography imaging limits the study’s diag-nostic scope,as these modalities offer superior capabilities in differentiating benign from malignant lesions and assessing metabolic tumor activity.Addi-tionally,the retrospective,cross-sectional design restricts the potential for dyna-mic insights into disease progression.We also highlight the untapped potential of radiomics-based analyses,which could significantly improve diagnostic accuracy and prognostic assessments.We recommend integrating these advanced imaging modalities,adopting longitudinal study designs,and leveraging radiomics app-roaches in future research to enhance the diagnostic frameworks in pancreatic cancer imaging.
文摘Pancreatic cancer is one of the solid tumors with the worst prognosis.Five-year survival rate is less than 10%.Surgical resection is the only potentially curative treatment,but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients.Moreover,surgery is still associated with high post-operative morbidity,while other therapies still offer very disappointing results.This article reviews every aspect of pancreatic cancer,focusing on the elements that can improve prognosis.It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.
基金Supported by the Department of Biotechnology,Government of India,Ramalingaswami Reentry Fellowship,No.RLS/BT/Reentry/05/2012Department of Higher,Education,Science&Technology and Biotechnology,Government of West Bengal,India,No.BT/P/Budget/RD-37/2016.
文摘Pancreatic cancer(PanCa)is a catastrophic disease,being third lethal in both the genders around the globe.The possible reasons are extreme disease invasiveness,highly fibrotic and desmoplastic stroma,dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics.This inimitable tumor microenvironment(TME)or desmoplasia with excessive extracellular matrix accumulation,create an extremely hypovascular,hypoxic and nutrient-deficient zone inside the tumor.To survive,grow and proliferate in such tough TME,pancreatic tumor and stromal cells transform their metabolism.Transformed glucose,glu-tamine,fat,nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism,impart therapy resistance,and immunosuppression in PanCa.Thus,a finer knowledge of altered metabolism would uncover its metabolic susceptibilities.These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa.In this review,we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
基金Guangdong Basic and Applied Basic Research Foundation,No.2019A1515011609Project of Educational Commission of Guangdong Province of China,No.2018KQNCX124Guangzhou Science and Technology Key Point Project,No.202103000041.
文摘BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.
基金Supported by National Natural Science Foundation of China,No.82100581。
文摘BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,often failing to capture the complexity of the disease.The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment.This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer.AIM To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules.METHODS This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2,PLAU,and CCNA2.The results were validated in an independent dataset.This study also examined the correlations between the model risk score and various clinical features,components of the immune microenvironment,chemotherapeutic drug sensitivity,and metabolism-related pathways.Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines.RESULTS The prognostic model demonstrated significant predictive value,with the risk score showing a strong correlation with clinical features:It was significantly associated with tumor grade(G)(bP<0.01),moderately associated with tumor stage(T)(aP<0.05),and significantly correlated with residual tumor(R)status(bP<0.01).There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs.Furthermore,the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer.CONCLUSION The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.
基金Supported by Health Commission of Qinghai Province,No.2021-wjzdx-18.
文摘BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.
文摘BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.
基金Supported by Medicine and Health Science and Technology Project of Zhejiang Province,No.2021KY168.
文摘BACKGROUND Systemic inflammation and nutrition play pivotal roles in cancer progression and can increase the risk of delayed recovery after surgical procedures.AIM To assess the significance of inflammatory and nutritional indicators for the prognosis and postoperative recovery of patients with pancreatic cancer(PC).METHODS Patients who were diagnosed with PC and underwent surgical resection at our hospital between January 1,2019,and July 31,2023,were enrolled in this retrospective observational cohort study.All the data were collected from the electronic medical record system.Seven biomarkers-the albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune–inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index(NRI),and geriatric NRI were assessed.RESULTS A total of 446 patients with PC met the inclusion criteria and were subsequently enrolled.Patients with early postoperative discharge tended to have higher PNI values and lower SII,NLR,and PLR values(all P<0.05).Through multivariable logistic regression analysis,the SII value emerged as an independent risk factor influencing early recovery after surgery.Additionally,both univariable and multivariable Cox regression analyses revealed that the PNI value was the strongest prognostic marker for overall survival(OS;P=0.028)and recurrence-free survival(RFS;P<0.001).The optimal cutoff PNI value was established at 47.30 using X-tile software.Patients in the PNI-high group had longer OS(P<0.001)and RFS(P=0.0028)times than those in the PNI-low group.CONCLUSION Preoperative systemic inflammatory-nutritional biomarkers may be capable of predicting short-term recovery after surgery as well as long-term patient outcomes.
文摘The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial disparities and risk factors.Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients.The study,which included 14.2 million admissions from 2016-2017,found that 2.6%of adult patients were diagnosed with CP,with white males being the majority.Multivariate regression analysis identified men,black individuals,those aged 40-59 years,and individuals with a body mass index(BMI)between 25 and 29.9 as having an increased risk for CP.Moreover,0.78%of CP patients also had PDAC,with older age and BMI being significant risk factors for developing PDAC in CP patients.The study also highlighted disparities in healthcare access and utilization among different socioeconomic and ethno-racial groups,which may impact the risk and outcomes of CP and PDAC.
