Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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.

Metastatic clear cell sarcoma of the pancreas:A sporadic cancer

Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

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.

Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location

BACKGROUND A growing body of research indicates significant differences between left-sided colon cancers(LCC)and right-sided colon cancers(RCC).Pan-immune-inflammation value(PIV)is a systemic immune response marker that can predict the prognosis of patients with colon cancer.However,the specific distinction between PIV of LCC and RCC remains unclear.AIM To investigate the prognostic and clinical significance of PIV in LCC and RCC patients.METHODS This multicenter retrospective cohort study included 1510 patients with colon cancer,comprising 801 with LCC and 709 with RCC.We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival(DFS)in these patients.Kaplan-Meier analysis,as well as univariate and multivariate analyses,were used to examine the risk factors for DFS.The correlation between PIV and the clinical characteristics was statistically analyzed in these patients.RESULTS A total of 1510 patients{872 female patients(58%);median age 63 years[interquartile ranges(IQR):54-71];patients with LCC 801(53%);median follow-up 44.17 months(IQR 29.67-62.32)}were identified.PIV was significantly higher in patients with RCC[median(IQR):214.34(121.78-386.72)vs 175.87(111.92-286.84),P<0.001].After propensity score matching,no difference in PIV was observed between patients with LCC and RCC[median(IQR):182.42(111.88-297.65)vs 189.45(109.44-316.02);P=0.987].PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC.High PIV(>227.84)was associated with worse DFS in LCC[PIV-high:Adjusted hazard ratio(aHR)=2.39;95%confidence interval:1.70-3.38;P<0.001]but not in RCC(PIV-high:aHR=0.72;95%confidence interval:0.48-1.08;P=0.114).CONCLUSION These findings suggest that PIV may predict recurrence in patients with LCC but not RCC,underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。

Local recurrence rate as quality indicator in surgery for pancreatic cancer?

To the Editor: As we all know, even with the current advancements regarding novel chemotherapy regimens, patients affected by pancreatic cancer(PC) have an extremely dismal prognosis(5-year survival rate 12% for all stages in the National Cancer Institute SEER database). Among the patients undergoing surgical treatment, the prognosis is mostly affected by recurrence. PC after surgery has mainly four patterns of recurrence, isolated or variously associated with each other: local, lymph nodal, peritoneal or distant(liver, lung, other sites).

Pancreatic cancer with gastrointestinal obstruction as an initial symptom

To the Editor: Pancreatic cancer is the fourth leading cause of cancer mortality in the United States [ 1, 2 ]. Risk factors of pancreatic cancer include smoking, family history of chronic pancreatitis, advanced age, male, diabetes mellitus, and obesity [1]. Most of patients have no obvious symptoms in the early stage, and are often diagnosed in the late stage and accompanied by invasion of surrounding tissues and distant metastasis, such as local lymph nodes, liver, lung and peritoneum [ 1, 3 ]. Therefore, the prognosis is poor.

Nursing Care and Causative Analysis of Grade IV Capsular Contracture Following Breast Cancer Expander Implantation

Objective: By observing the treatment and nursing care of a patient with Grade IV capsular contracture following breast cancer expander implantation and subsequent Stage II reconstruction, we aim to analyze the reasons for the formation of capsular contracture after Stage I expander implantation and prevent its recurrence following Stage II reconstruction. Methods: In May 2020, the patient noticed an increase in the size of a breast mass. In August, she underwent AC-THP neoadjuvant chemotherapy, followed by a “right breast-conserving nipple-areolar subglandular excision + right axillary lymph node dissection + expander implantation” surgery in November 2020. Radiation therapy began in January 2021. During radiation therapy, the patient experienced severe breast hardening, distortion, tenderness, and was diagnosed with Grade IV capsular contracture. To relieve the capsular contracture, the patient underwent a “contracted capsule incision and release procedure + removal of the right breast expander + right breast implantation” surgery in July 2021. Postoperatively, measures were taken to prevent incision infection, emphasizing aseptic techniques, ensuring smooth negative pressure drainage, reducing skin flap tension, monitoring skin flap blood supply, actively preventing subcutaneous effusion and hematoma, and applying appropriate compression dressings. Results: The patient was discharged after the removal of the drainage tube. During the postoperative follow-up at 3 and 6 months, there was no recurrence of capsular contracture, and the breast appeared full, upright, and relatively soft. There were no complications such as hematoma, infection, breast implant rupture, breast sagging, or displacement. The patient had a good outcome without additional financial or surgical burdens. Conclusion: The occurrence of Grade IV capsular contracture in the patient is generally related to infection after Stage I expander implantation, improper compression dressing, excessive saline injection causing content infiltration, and radiation therapy. Therefore, it is recommended to enhance the intraoperative and postoperative prophylactic use of antibiotics after Stage I expander implantation. Intermittent saline injection after surgery, with the amount of saline gradually increasing rather than filling all at once, is advisable. This helps the breast tissue gradually adapt to expansion, reducing the risk of capsular contracture. Postoperatively, patients should be instructed to wear pressure garments and breast elastic bandages while intensifying breast monitoring during radiation therapy and increasing postoperative follow-up.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Clear cell sarcoma of the pancreas,an unusual cancer with unusual metastatic site or unusual primary site?

Clear cell sarcoma(CCS)is a type of malignant tumor that can arise from tendons and aponeuroses.This malignant proliferation of cells with melanocytic lineage normally occurs in young patients,and it is normally identified in extremities.However,different sites including gastrointestinal organs are also described.Due difficulties in the molecular and histopathology evaluation,the diagnosis is often confused with malignant melanoma.Most cases are treated with surgical resection,but overall,the prognosis is poor.In this editorial,we will discuss a very interesting case of CCS identified in the pancreas.We will discuss the literature and controversies in the management of this type of cancer.Furthermore,we will address molecular strategies to be incorporated in those cases to better understand the primary location of the tumor.Finally,future perspectives of the field and new strategies of treatment will be described.

Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50%,major complications 0%/100%,anastomotic leaks 0%/100%,3-year DFS and OS 66.67%(gastric carcinoma)and 0%(oesophagus).Twenty breast cancer without deaths/major complications;3-year OS 100%and DFS 85%.Nobody contracted SARS-CoV-2 postoperatively.COVID-19 pandemic–related changes:78.2%treated in alternative buildings,43.8%waited more than 4 weeks,two additional colostomies and fewer laparoscopies.CONCLUSION Some patients lost curative-intent surgery due to COVID-19 pandemic.Despite practice modifications and 43.8%delays higher than 4 weeks,surgery was resumed with minimal changes without impacting outcomes.Clean pathways are essential to continue surgery safely.

Evaluation of Colorectal Cancer Management in Eastern DR Congo. About 55 Cases Were Collected from January 2002 to December 2016 Panzi General Referral Hospital

A retrospective study was conducted at the HGR de Panzi in eastern DR Congo to determine the profile of colorectal cancer (CRC) management based on 55 cases out of 129 digestive cancers diagnosed in the digestive surgery, endoscopy, and pathology department of the HGR de Panzi from January 2002 to December 2016. The prevalence of CRC was 42.6%. The mean age of patients was 50.8 years, with a range of 20 to 81 years. The male to female ratio was 2.2. In 69.1% of cases, the patients had a low socioeconomic status, and 52.7% had a history of hemorrhoids. Rectorrhagia revealed CCR in 49.1% of cases. The mode of discovery was predominantly emergency in 69.1% of cases, and 58.20% of CRCs were diagnosed by an initial endoscopy of the lower colon. Adenocarcinoma was found in 94.5% of cases, and 45% of cases required abdominoperineal amputation. Various postoperative complications were experienced by 54.5% of patients, and 25.5% of patients died. To decrease the occurrence of these types of cancers, it is necessary to focus on early detection in the population and enhance access to primary healthcare for everyone.

Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge

Diagnosing early-stage pancreatic cancer(PC)remains a clinical challenge.Hence,studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative.This article aims to un-derscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC,thereby improving its management and prognosis.

Bibliometric analysis of olaparib and pancreatic cancer from 2009 to 2022:A global perspective

BACKGROUND Genetic screening for breast cancer gene 1(BRCA)1/2 mutations can inform breast/ovarian/pancreatic cancer patients of suitable therapeutic interventions.Four to seven percent of pancreatic cancer patients have germline BRCA mutations.BRCA genes aid in DNA repair,especially homologous recombination,which impacts genomic stability and cancer cell growth.BRCA1 regulates the cell cycle,ubiquitination,and chromatin remodeling,whereas BRCA2 stimulates the immune response.They predict the efficacy of platinum chemotherapy or polymerase(PARP)inhibitors such as olaparib.AIM To determine the trends and future directions in the use of olaparib for pancreatic cancer treatment.METHODS To evaluate the trends in how olaparib works in pancreatic cancer,we performed a bibliometric analysis.One hundred and ninety-six related publications were accessed from the Web of Science Core Collection and were published between 2009 and 2022.The analytic parameters included publications,related citations,productive countries and institutes,influential authors,and keyword development.RESULTS This study visualizes and discusses the current research,including the present global trends and future directions in olaparib and pancreatic cancer.Overall,this study sheds light on optimizing the use of olaparib in pancreatic cancer treatment,Feng X et al.The use of olaparib in pancreatic cancer WJGO https://www.wjgnet.com 4490 November 15,2024 Volume 16 Issue 11 offering valuable guidance for researchers in this field.CONCLUSION Our findings identified trends in olaparib and pancreatic cancer,with China and the USA leading and with global cooperation tightening.O'Reilly EM's team and Memorial Sloan-Kettering had the highest output.The Journal of Clinical Oncology was the most cited journal.More PARP inhibitors are emerging,and combination therapy is suggested for future therapeutic trends.

Impact of the COVID-19 Pandemic on Cancer Patients: Experience of the medical oncology department of CHU HASSAN II Fez.

Introduction: In December 2019, COVID 19 spread worldwide, but did not officially start in MOROCCO until March 02, 2020. Since then, this pandemic has significantly impacted the health status of patients in general and cancer patients in particular. The main objective of our study is to evaluate the prognosis of patients treated for cancer and infected with COVID-19. Material and method: A descriptive study with prospective collection was carried out at the medical oncology department of CHU Hassan II in FEZ over a period of two years, from March 2020 to March 2022. Data was carried out on the software SPSS. Results: One hundred cancer patients tested positive for COVID-19 infection and were collected within our department. The average age was 56 years [22-91]. The sex ratio was 1.2. Patients with breast cancer were the most affected by this infection (34%). The clinical symptomatology was dominated by the respiratory syndrome (45%).The diagnosis was made through thoracic CT scan in 62% of cases. 76% of patients were in a metastatic stage. 96% of patients were undergoing oncological treatment. For symptomatique patients, the standard treatment approach involved using antibiotics in 76% of cases. Evolution was marked by recovery in 79% of patients, with a death rate of 12% in this cancer patient population. Conclusion: COVID-19 infection is particularly severe in cancer patients. Mortality among these patients remains high and is associated with overall patient characteristics. However, anticancer treatments have not shown deleterious effects on the course of COVID-19.

Targeting KRAS in pancreatic cancer

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient therapies.The Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for therapy.However,the most common KRAS mutations in PDAC are G12D(44%),G12V(34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung cancer.KRAS G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of PDAC.Recently,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in development.The other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(GEF)Son of Sevenless 1 that drives KRAS.These agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

Identification of Prognosis-Related Genes and Key Target Genes for Pancreatic Cancer: A Bioinformatics Analysis

Objective: The mortality and morbidity rates associated with pancreatic cancer (PaCa) are extremely high. Various studies have demonstrated that pancreatic cancer will be the fourth cancer-related death by 2030, raising more concern for scholars to find effective methods to prevent and treat in order to improve the pancreatic cancer outcome. Using bioinformatic analysis, this study aims to pinpoint key genes that could impact PaCa patients’ prognosis and could be used as therapeutic targets. Methods: The TCGA and GEO datasets were integratively analyzed to identify prognosis-related differentially expressed genes. Next, the STRING database was used to develop PPI networks, and the MCODE and CytoNCA Cytoscape in Cytoscape were used to screen for critical genes. Through CytoNCA, three kinds of topology analysis were considered (degree, betweenness, and eigenvector). Essential genes were confirmed as potential target treatment through Go function and pathways enrichment analysis, a developed predictive risk model based on multivariate analysis, and the establishment of nomograms using the clinical information. Results: Overall, the GSE183795 and TCGA datasets associated 1311 and 2244 genes with pancreatic cancer prognosis, respectively. We identified 132 genes that were present in both datasets. The PPI network analysis using, the centrality analysis approach with the CytoNCA plug-in, showed that CDK2, PLK1, CCNB1, and TOP2A ranked in the top 5% across all three metrics. The independent analysis of a risk model revealed that the four key genes had a Hazard Ratio (HR) > 1. The monogram showed the predictive risk model and individual patient survival predictions were accurate. The results indicate that the effect of the selected vital genes was significant and that they could be used as biomarkers to predict a patient’s outcome and as possible target therapy in patients with pancreatic cancer. GO function and pathway analysis demonstrated that crucial genes might affect the P53 signaling pathway and FoxO signaling pathway, through which Meiotic nuclear division and cell cycle may have a significant function in essential genes affecting the outcome of patients who have pancreatic cancer. Conclusions: This study suggests that CDK2, CCNB1, PLK1 and TOP2A are four key genes that have a significant influence on PaCa migration and proliferation. CDK2, CCNB1, PLK1, and TOP2A can be used as potential PaCa prognostic biomarkers and therapeutic targets. However, experimental validation is necessary to confirm these predictions. Our study comes into contributions to the development of personalized target therapy for pancreatic cancer patients.

Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts

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.

Advancements in breath-based diagnostics for pancreatic cancer:Current insights and future perspectives

Recent decades have seen a concerning surge in carcinogenic diseases,with cancer cases and deaths on the rise globally.Conventional diagnostic methods are often invasive and time-consuming,highlighting the need for fast,accurate,and painless alternatives.Non-invasive exhaled breath analysis emerges as a promising solution,with over 200 volatile organic compounds(VOCs)detected in exhaled air,showing potential as biomarkers for various diseases,including cancer.Despite the lack of standardized methodologies,advancements in analytical instruments have expanded detection capabilities,reaching 3500 VOCs.Studies have identified specific VOC patterns associated with different cancers,offering hope for non-invasive diagnosis.Techniques such as gas chromatography-mass spectrometry and electronic noses show promise in distinguishing between healthy individuals and cancer patients.However,further research and standardization are needed to realize the full clinical potential of breath-based diagnostics,particularly in the early detection of challenging cancers like pancreatic cancer.