Automated classification of urine biomarkers to diagnose pancreatic cancer using 1-D convolutional neural networks

Journal of Biological Engineering, Journal Year: 2023, Volume and Issue: 17(1)

Published: April 17, 2023

Abstract Background Early diagnosis of Pancreatic Ductal Adenocarcinoma (PDAC) is the main key to surviving cancer patients. Urine proteomic biomarkers which are creatinine, LYVE1, REG1B, and TFF1 present a promising non-invasive inexpensive diagnostic method PDAC. Recent utilization both microfluidics technology artificial intelligence techniques enables accurate detection analysis these biomarkers. This paper proposes new deep-learning model identify urine for automated pancreatic cancers. The proposed composed one-dimensional convolutional neural networks (1D-CNNs) long short-term memory (LSTM). It can categorize patients into healthy pancreas, benign hepatobiliary disease, PDAC cases automatically. Results Experiments evaluations have been successfully done on public dataset 590 samples three classes, 183 pancreas samples, 208 disease 199 samples. results demonstrated that our 1-D CNN + LSTM achieved best accuracy score 97% area under curve (AUC) 98% versus state-of-the-art models diagnose cancers using Conclusion A efficient 1D CNN-LSTM has developed early four TFF1. showed superior performance other machine learning classifiers in previous studies. prospect this study laboratory realization deep classifier urinary biomarker panels assisting procedures

Language: Английский

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Development of a Novel Anti-CD44 Variant 5 Monoclonal Antibody C44Mab-3 for Multiple Applications against Pancreatic Carcinomas

Antibodies, Journal Year: 2023, Volume and Issue: 12(2), P. 31 - 31

Published: April 28, 2023

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and resistance conventional chemotherapy. CD44 has been known as stem cell marker plays tumor promotion drug roles in various cancers. In particular, splicing variants are overexpressed many carcinomas play essential stemness, invasiveness or metastasis, treatments. Therefore, understanding each variant’s (CD44v) function distribution is for establishment CD44-targeting therapy. this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary (CHO)-K1 cells established anti-CD44 monoclonal antibodies (mAbs). One clones (C44Mab-3; IgG1, kappa) recognized peptides variant-5-encoded region, indicating that C44Mab-3 specific mAb CD44v5. Moreover, reacted CHO/CD44v3–10 pancreatic lines (PK-1 PK-8) by flow cytometry. The apparent KD PK-1 was 1.3 × 10−9 M 2.6 M, respectively. could detect exogenous CD44v3–10 endogenous CD44v5 Western blotting stained formalin-fixed paraffin-embedded but not normal epithelial immunohistochemistry. These results indicate useful detecting applications expected be application diagnosis

Language: Английский

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A Cancer-Specific Monoclonal Antibody against Podocalyxin Exerted Antitumor Activities in Pancreatic Cancer Xenografts

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 161 - 161

Published: Dec. 21, 2023

Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL involved tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, considered a promising target monoclonal antibody (mAb)-based therapy. However, also plays an essential role normal cells, such as vascular lymphatic endothelial cells. cancer specificity or selectivity required to reduce adverse effects on Here, we developed anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG1, kappa), by immunizing mice soluble ectodomain derived from glioblastoma LN229 cell. reacted PODXL-positive cells but not PODXL-knockout flow cytometry. Importantly, recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, PK-45H) did react (LECs). In contrast, one non-CasMabs, PcMab-47, showed high reactivity both PDAC LECs. Next, engineered into mouse IgG2a-type (PcMab-6-mG2a) humanized IgG1-type (humPcMab-6) further produced core fucose-deficient types (PcMab-6-mG2a-f humPcMab-6-f, respectively) potentiate antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG2a-f humPcMab-6-f exerted ADCC complement-dependent presence effector complements, respectively. xenograft model, exhibited potent antitumor effects. These results indicated that could apply antibody-based therapy against PODXL-expressing cancers.

Language: Английский

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Histological variants of pancreatic ductal adenocarcinoma: a survival analysis

Langenbeck s Archives of Surgery, Journal Year: 2024, Volume and Issue: 409(1)

Published: Oct. 19, 2024

Abstract Purpose Pancreatic ductal adenocarcinoma (PDAC) can be classified into distinct histological subtypes based on the WHO nomenclature. The aim of this study was to compare prognosis conventional PDAC (cPDAC) against other variants at population level. Methods Surveillance, Epidemiology and End Results (SEER) database used identify patients with microscopically confirmed PDAC. These were divided 9 subgroups. Overall survival assessed using Kaplan-Meier method Cox regression models stratified by tumor histology. A total 159,548 identified, whom 95.9% had cPDAC, followed colloid carcinoma (CC) (2.6%), adenosquamous (ASqC) (0.8%), signet ring cell (SRCC) (0.5%), undifferentiated (UC) (0.1%), osteoclast-like giant cells (UCOGC) hepatoid (HC) (0.01%), medullary pancreas (MCP) (0.006%) pancreatic rhabdoid phenotype (PUCR) (0.003%). curves showed that PUCR worst (median survival: 2 months; 5-year 0%), while MCP best 41 33.3%). In a multivariable model, several (i.e. CC, ASqC, SRCC, UCOGC) identified as independent predictors overall when compared cPDAC. Conclusion is heterogenous disease accurate identification variant histology important for risk stratification, these may have different biological behavior.

Language: Английский

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Novel Insights into T-Cell Exhaustion and Cancer Biomarkers in PDAC Using Single Cell RNA Sequencing

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract One of the aggressive and lethal cancers, pancreatic ductal adenocarcinoma (PDAC) is characterised by poor prognosis resistance to conventional treatments. Moreover, tumor immune microenvironment (TIME) plays a crucial role in progression therapeutic PDAC. It associated with T-cells exhaustion, leading progressive loss T-cell functions impaired ability kill cells. Therefore, this study employed single cell RNA sequencing (scRNA-seq) analysis identified upregulated genes cancer cells two groups (“cancer cells_vs_all-PDAC” “cancer-PDAC_vs_all-normal”), while T-cells, including CD8+ NKT-like cells, memory CD4+ naive were between conditions (PDAC_vs_Normal) their respective types. Subsequently, common unique markers from both identified, resulting three sub-groups (common groups, “cancer “cancer-PDAC_vs_all-normal” group). top-10 enriched Reactome pathways unique) identified; implicated those selected perform PPI analysis, eventually revealing hub-genes each group ( GAPDH, AKT1, EGFR, CS, RHOA, TPI1, SDHA, TFRC, FASN, HIF1A, H4C6, MYC, H3C12, DDX21, USP7, RFC4, APEX1, CDK9, H2BC9, NOP2, FN1, COL1A1, COL1A2, COL3A1, COL5A2, COL6A1, COL5A1, BGN, COL6A2, FBN1 ) ACTB, CD4, CTNNB1, H3-3B, HSP90AA1, HSP90AB1, HSPA8, IFNG, ITGB1, JUN, MAPK3, MMP9, NFKB1, TP53, UBB, UBC ). Furthermore, gene expression validation was performed using GEPIA2 TISCH2, overall survival GEPIA2. Conclusively, unravelled total 16 novel UBC, H3-3B indicating that these might be rendering growth, proliferation, This provides groundwork for future research into landscape PDAC, particularly exhaustion. However, further clinical studies are needed validate as potential targets PDAC patients.

Language: Английский

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Identification of key regulators in pancreatic ductal adenocarcinoma using network theoretical approach

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0313738 - e0313738

Published: Jan. 27, 2025

Pancreatic Ductal Adenocarcinoma (PDAC) is a devastating disease with poor clinical outcomes, which mainly because of delayed detection, resistance to chemotherapy, and lack specific targeted therapies. The disease’s development involves complex interactions among immunological, genetic, environmental factors, yet its molecular mechanism remains elusive. A major challenge in understanding PDAC etiology lies unraveling the genetic profiling that governs network. To address this, we examined gene expression profile compared it healthy controls, identifying differentially expressed genes (DEGs). These DEGs formed basis for constructing protein interaction network, their network topological properties were calculated. It was found self-organizes into scale-free fractal state weakly hierarchical organization. Newman Girvan’s algorithm (leading eigenvector (LEV) method) community detection enumerated four communities leading at least one motif defined by G (3,3). Our analysis revealed 33 key regulators predominantly enriched neuroactive ligand-receptor interaction, Cell adhesion molecules, Leukocyte transendothelial migration pathways; positive regulation cell proliferation, kinase B signaling biological functions; G-protein beta-subunit binding, receptor binding functions etc. Transcription Factor mi-RNA obtained. Recognizing therapeutic potential biomarker significance Key regulators, also identified approved drugs genes. However, imperative subject experimental validation establish efficacy context PDAC.

Language: Английский

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Gemcitabine Alters Phosphatidylcholine Metabolism in Mouse Pancreatic Tumors

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest diseases, despite advancements in elucidating tumor biology and developing novel therapeutics. Importantly, lipids, such as phospholipids, are crucial for survival proliferation of cells. However, impact chemotherapeutic drugs on phospholipid metabolism PDAC remains poorly understood. Gemcitabine (a nucleoside analogue) a first-line drug treatment, but its clinical effectiveness limited by multiple factors. Herein, we employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) proteomics approaches to investigate gemcitabine-induced lipid alterations mouse pancreatic tumors following gemcitabine treatment (n = 3, control tumors; n gemcitabine-treated tumors). From MALDI MSI experiments, observed elevated levels several phosphatidylcholines (PCs), PC(30:0), PC(32:3), PC(34:2), PC(36:1), PC(36:2), tissues compared control. In addition, data revealed differential abundance phospholipid-binding proteins response treatments. Furthermore, endoplasmic reticulum stress-related exhibited high expression tissues. Altogether, our provide important insights into PC treatment. targeting altered during therapy might help combat cancer.

Language: Английский

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Anticancer Potential of Lyophilised Medicinal Leech (Hirudo verbana) of Saliva Extract Against Pancreatic Cancer (MIA PaCa-2) Cell Lines

Journal of Anatolian Environmental and Animal Sciences, Journal Year: 2025, Volume and Issue: 10(2), P. 167 - 173

Published: March 15, 2025

Cancer is the second leading cause of death worldwide, after cardiovascular disease. It can affect any part body and spread to other organs. Pancreatic cancer a tough disease diagnose treat. fourteenth most common seventh deadliest worldwide. New technology innovative methods, combined with range therapeutic agents, have led promising new anticancer treatments. The presence various bioactive components in secretions medicinal leeches has prompted re-evaluation these organisms as popular method traditional medicine. In this study, effect potential Lyophilised leech secretion on pancreatic cell line (MIA PaCa-2) was investigated using XTT assay. A viability test conducted ascertain degree cytotoxicity following administration varying concentrations lines over period 24, 48, 72 hours. percentage cells determined at each concentration. doses were adjusted dilution procedures ratios 75 µg/ml, 150 300 600 1200 µg/ml. IC50 value 24th hour: 484.48 µg/ml; 48th 330.92 72nd 542,75 observed that Hirudo verbana not linear. µg/ml extracts had cytotoxic anti-proliferative effects. These results indicate saliva extract anti proliferative effects may role developing drugs.

Language: Английский

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Development of a Novel Anti-CD44 Variant 5 Monoclonal Antibody C₄₄Mab-3 for Multiple Applications against Pancreatic Carcinomas

Published: Jan. 31, 2023

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and resistance conventional chemotherapy. CD44 has been known as stem cell marker, plays tumor promotion drug in various cancers. Especially, splicing variants are overexpressed many carcinomas, play essential roles stemness, invasiveness or metastasis, treatments. Therefore, understanding each variant (CD44v) function distribution carcinomas is for establishment CD44-targeting therapy. In this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells, established anti-CD44 monoclonal antibodies (mAbs). One clones (C44Mab-3; IgG1, kappa) recognized peptides 5-encoded region, indicating that C44Mab-3 specific mAb CD44v5. Moreover, reacted CHO/CD44v3–10 cells pancreatic lines (PK-1 PK-8) by flow cytometry. The apparent KD PK-1 was 7.1 × 10−10 M 1.9 10−9 M, respectively. could detect exogenous CD44v3–10 endogenous CD44v5 western blotting, stained formalin-fixed paraffin-embedded but not normal epithelial immunohistochemistry. These results indicate useful detecting applications, expected application diagnosis

Language: Английский

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Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(20), P. 6461 - 6461

Published: Oct. 11, 2023

Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks advances in chemo/radiotherapy and the reduction operative mortality.This narrative review presents a chosen literature selection, giving picture of current state treatment these patients.Neoadjuvant therapy (NAT) is generally recognized as choice before surgery. However, despite increased efficacy, best pathological response still limited 10.9-27.9% patients. There data on selection possible NAT responders how diagnose non-responders early. Multidetector computed tomography has high sensitivity low specificity evaluating resectability after NAT, limiting resection rate Ca 19-9 Positron emission promising results. The prediction early recurrence radical metastatic PDAC, thus identifying with poor prognosis saving them from little benefit, ongoing, although some available.In conclusion, high-level evidence demonstrating benefit surgical such lacking should not be performed outside high-volume centers interdisciplinary teams surgeons oncologists.

Language: Английский

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