The RAGE Inhibitor TTP488 (Azeliragon) Demonstrates Anti-Tumor Activity and Enhances the Efficacy of Radiation Therapy in Pancreatic Cancer Cell Lines DOI Open Access
Kumari Alka, Jacob F. Oyeniyi, Ghulam Mohammad

et al.

Cancers, Journal Year: 2024, Volume and Issue: 17(1), P. 17 - 17

Published: Dec. 24, 2024

Pancreatic cancer is the third leading cause of cancer-related mortality in United States, with rising incidence and mortality. The receptor for advanced glycation end products (RAGE) its ligands significantly contribute to pancreatic progression by enhancing cell proliferation, fostering treatment resistance, promoting a pro-tumor microenvironment via activation nuclear factor-kappa B (NF-κB) signaling pathways. This study validated pathway human evaluated therapeutic efficacy TTP488 (Azeliragon), small-molecule RAGE inhibitor, alone combination radiation therapy (RT) preclinical models cancer. Human (Panc1) murine (Pan02) lines exhibited elevated levels compared normal tissue. In vitro, Azeliragon inhibited RAGE-mediated NF-κB ligand-mediated proliferation lines. Target engagement was confirmed vivo, as determined decreased activation. demonstrated significant growth delay mouse additive effects when combined RT. Additionally, modulated immune suppressive tumor reducing immunosuppressive cells, including M2 macrophages, regulatory T myeloid-derived suppressor while CD8+ infiltration. These findings suggest that Azeliragon, inhibiting modulating response, may serve an effective anti-cancer agent

Language: Английский

Patient‐derived xenograft model in cancer: establishment and applications DOI Creative Commons

Ao Gu,

Jiatong Li, Mengyao Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 19, 2025

Abstract The patient‐derived xenograft (PDX) model is a crucial in vivo extensively employed cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, diverse treatment histories. Various strategies utilized PDX models can offer valuable insights into mechanisms tumor progression, drug resistance, development novel therapies. This review provides comprehensive overview establishment applications models. We present an history current status models, elucidate construction methodologies for different tumors, conduct comparative analysis highlight distinct advantages limitations this relation other are elucidated domain comprehending underlying therapy, which highlights broad fields chemotherapy, targeted delivery systems, combination antibody–drug conjugates radiotherapy. Furthermore, with multiomics single‐cell analyses also emphasized. application clinical personalized medicine additionally

Language: Английский

Citations

5
Immunotherapeutic Potential of the Yellow Fever Virus Vaccine Strain 17D for Intratumoral Therapy in a Murine Model of Pancreatic Cancer DOI Creative Commons
Alina S. Nazarenko, Yulia K. Biryukova, Kirill N. Trachuk

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(1), P. 40 - 40

Published: Jan. 6, 2025

Objective: We evaluate the immunotherapeutic potential of yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy pancreatic cancer in mice. Methods: The cytopathic effect YFV on mouse syngeneic cancers cells were studied both vitro and vivo human vitro. Results: demonstrated a strong against Although did not exhibit lytic Pan02 vitro, single administration caused delay tumor growth an increase median survival by 30%. Multiple injections further improve growth; however, it notably extended survival. Furthermore, preliminary immunization with enhanced its oncotherapeutic effect. Conclusions: Intratumoral delayed murine model cancer. fact that affected much more strongly than appears promising. Hence, we anticipate efficacy YFV-17D-based oncolytic will also be higher carcinomas compared to tumor.

Language: Английский

Citations

0
Utility of Polygenic Risk Scores (PRSs) in Predicting Pancreatic Cancer: A Systematic Review and Meta-Analysis of Common-Variant and Mixed Scores with Insights into Rare Variant Analysis DOI Open Access
Georgios‐Ioannis Verras, Zaed Hamady, Andrew Collins

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 241 - 241

Published: Jan. 13, 2025

Pancreatic adenocarcinoma is the most common histological subtype of pancreatic cancer, representing approximately 85% all cases [...]

Language: Английский

Citations

0
Advancing Pancreatic Cancer Prediction with a Next Visit Token Prediction Head on Top of Med-BERT DOI Open Access
Jianping He, Laila Rasmy, Degui Zhi

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 516 - 516

Published: Feb. 4, 2025

Background: Electronic Health Records (EHRs) encompass valuable data essential for disease prediction. The application of artificial intelligence (AI), particularly deep learning, significantly enhances prediction by analyzing extensive EHR datasets to identify hidden patterns, facilitating early detection. Recently, numerous foundation models pretrained on have demonstrated efficacy in using EHRs. However, there remains some unanswered questions how best utilize such models, especially with very small fine-tuning cohorts. Methods: We utilized Med-BERT, an EHR-specific model, and reformulated the binary task into a token next visit mask align Med-BERT’s pretraining format order improve accuracy pancreatic cancer (PaCa) both few-shot fully supervised settings. Results: reformulation task, referred as Med-BERT-Sum, slightly superior performance scenarios larger samples. Furthermore, reformulating Next Visit Mask Token Prediction (Med-BERT-Mask) outperformed conventional Binary Classification (BC) (Med-BERT-BC) 3% 7% sizes ranging from 10 500 These findings highlight that aligning downstream objectives substantially model’s predictive capabilities, thereby improving its effectiveness predicting rare common diseases. Conclusions: Reformatting tasks accuracy, leading earlier detection timely intervention. This approach improves treatment effectiveness, survival rates, overall patient outcomes PaCa potentially other cancers.

Language: Английский

Citations

0
Exosomal CD40, CD25, and Serum CA19-9 as Combinatory Novel Liquid Biopsy Biomarker for the Diagnosis and Prognosis of Patients with Pancreatic Ductal Adenocarcinoma DOI Open Access
Paul David,

Dina Kouhestani,

Frederik J. Hansen

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1500 - 1500

Published: Feb. 11, 2025

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is largely due to several challenges, such as late diagnosis, early metastasis, limited response chemotherapy, aggressive tumor biology, and high rates recurrence. Therefore, the development a non-invasive effective method for detection PDAC crucial improving patient outcomes. Continued research exploration in this area are essential enhance methods ultimately improve individuals with PDAC. In study, we examined 37 exosomal surface proteins through multiplex flow cytometry test on peripheral plasma samples from group 51 clinical control (including healthy volunteers non-cancer patients (Cholecystectomy, Hernia, volunteers)), 21 pancreatitis, 48 diagnosed Our findings revealed that level CD40 expression significantly lower pancreatitis compared (p < 0.0001). Additionally, exhibited higher levels CD25 than = 0.0104). exo-CD40 had worse survival 0.0035). Similarly, exo-CD25 showed comparison 0.04). Statistical analysis achieved an AUC 0.827 distinguishing controls. Combining along CA19-9 discriminated controls 0.92. Exo-CD40 found exosomes isolated can serve excellent biomarkers diagnosis Further larger scale studies needed validate combined diagnostic tool identification liquid biopsy.

Language: Английский

Citations

0
Administration of FOLFIRINOX for Advanced Pancreatic Cancer: Physician Practice Patterns During Early Use DOI Creative Commons
Joanna Gotfrit, Horia Marginean,

Yoo-Joung Ko

et al.

Current Oncology, Journal Year: 2025, Volume and Issue: 32(3), P. 128 - 128

Published: Feb. 25, 2025

Advanced pancreatic cancer results in high morbidity and mortality. The standard of care treatment the advanced setting changed 2011 with introduction FOLFIRINOX (FFX) chemotherapy. However, it was highly toxic significant risk complications. We assessed practice patterns medical oncologists across Canada. Methods: performed a retrospective study consecutive patients treated FFX at eight Canadian centers. Demographic, treatment, outcome data were collected analyzed. Results: median age 61 (range 24–80), 43% female, 96% had an ECOG PS 0 or 1, 50% three more metastatic sites. follow-up time 20.8 months (95%CI 18.6–24.9). Physicians started dose 31% time. prescribed GCSF for primary prophylaxis most when giving standard-dose (30% time) comparison to reduced without 5-FU bolus. Dose reductions occurred 78.1% patients, while delay 65.2% patients. Conclusions: Medical Canada historically fashion that not uniform, prior emergence evidence upfront reductions.

Language: Английский

Citations

0
Spatial Transcriptomics Reveals Novel Mechanisms Involved in Perineural Invasion in Pancreatic Ductal Adenocarcinomas DOI Open Access
Vanessa Lakis, Noni Chan,

Ruth J. Lyons

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 852 - 852

Published: March 1, 2025

Pancreatic ductal adenocarcinoma (PDAC) has a high incidence of perineural invasion (PNI), pathological feature the cancer nerves. PNI is associated with poor prognosis, local recurrence and pain. It been suggested that interactions between nerves tumor microenvironment (TME) play role in PDAC tumorigenesis. Here, we used Nanostring GeoMx Digital Spatial Profiler to analyze whole transcriptome both nerve cells non-PNI foci from 13 patients. We identified previously reported pathways involved PNI, including Axonal Guidance ROBO-SLIT Signaling. transcriptomics highlighted influencing immune landscape TME similarities injury response. This study revealed endocannabinoid polyamine metabolism may contribute growth Key members these can be targeted, offering potential novel research avenues for exploring new treatment and/or pain management options PDAC.

Language: Английский

Citations

0
Nonalcoholic fatty liver disease following laparoscopic duodenum-preserving pancreatic total head resection vs laparoscopic pancreaticoduodenectomy: A retrospective cohort study DOI
Tingting Zhen, Shizhen Li, Shutao Pan

et al.

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(13)

Published: April 2, 2025

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in individuals who do not consume alcohol. Several risk factors influencing onset NAFLD after laparoscopic pancreaticoduodenectomy (LPD) have been identified. This study investigated associated with development duodenum-preserving pancreatic total head resection (LDPPHRt) and LPD. AIM To compare effects LDPPHRt LPD on postoperative NAFLD. METHODS retrospective cohort included 59 patients were histologically diagnosed benign or low-grade malignant tumors underwent surgery (LDPPHRt LPD) between May 2020 April 2023. Patient data perioperative variables analyzed compared. Multivariate logistic regression was used to identify pre-, peri-, for NAFLD, statistical significance set at P < 0.05. RESULTS Of study, 17 (28.8%) developed within 6-12 months post-surgery. The incidence significantly higher group compared (40.0% vs 12.5%, = 0.022). Multivariable analysis identified surgical approach (compared as an independent protective factor against odds ratio 0.208 (95% confidence interval: 0.046-0.931; 0.040). CONCLUSION Our findings indicate that more effective than reducing which may inform decision-making optimize patient outcomes surgery.

Language: Английский

Citations

0
Heteroaryl Group Containing Trisubstituted Alkenes: Synthesis and Anti‐tumor Activity DOI
Jiatong Li,

Ao Gu,

Mengyao Li

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(11)

Published: Aug. 15, 2024

Abstract Pancreatobililary cancers are fatal solid tumors that pose a significant threat to human life. It is imperative investigate novel small molecule active compounds for controlling these cancers. Heterocyclic (e. g. gemcitabine) and multi‐substituted alkenes resveratrol) commonly applied in tumor treatment. Researchers have proposed the synthesis of new trisubstituted containing heteroaromatic rings by combining two scaffolds may be fresh strategy develop molecules. In this study, we utilized alkenyl bromide heteroaryl boronic acid as substrates, employing Suzuki coupling generate series triarylethylenes featuring nitrogen, oxygen, sulfur atoms. Through vitro experiments, results indicated some exhibited remarkable anti‐tumor efficacy IC50 [ 3be , GBC‐SD] =0.13 μM PANC‐1] =0.27 μM). The further demonstrated antitumor was dependent on heteroatom, π‐system, skeleton‐bonding site, substituent type.

Language: Английский

Citations

3
Exploration of Dan-Shen-Yin against pancreatic cancer based on network pharmacology combined with molecular docking and experimental validation DOI Creative Commons

Ao Gu,

Jiatong Li,

Jian-An Wu

et al.

Current Research in Biotechnology, Journal Year: 2024, Volume and Issue: 7, P. 100228 - 100228

Published: Jan. 1, 2024

Traditional Chinese Medicine (TCM) introduces a potentially effective strategy in the realm of cancer therapy, whereas network pharmacology provides reliable mechanism for clarifying complex interplay between active constituents and their corresponding targets. Although Dan-Shen-Yin (DSY) has demonstrated remarkable efficacy treatment various diseases, its potential anti-pancreatic effects underlying mechanisms remain unexplored. The present study aims to validate DSY both vivo vitro, while also elucidating through combination pharmacology, molecular docking, related experiments. effectiveness was validated using patient-derived xenograft (PDX) model, which chosen due capacity maintain essential histological genetic attributes primary tumor. Network predicted DSY, confirmed by vitro experiments showing inhibitory on proliferation, pro-apoptosis, migration, colony formation PC cells. Molecular docking studies further that components exhibited good nucleophilicity selected target proteins ability interact via hydrogen bonding Van der Waals forces. PDX model showed effectively inhibited tumor growth improved prognosis. Experiments conducted have is an PC. Moreover, mechanistic investigations provided evidence impede EGFR/SRC/STAT3 signaling pathway.

Language: Английский

Citations

2