Publications by authors named "Rita T Lawlor"
Article Synopsis
- Fibroblast heterogeneity significantly impacts cancer progression, making it crucial to understand different fibroblast types for developing effective cancer treatments.
- In pancreatic ductal adenocarcinoma (PDAC), cancer-associated fibroblasts (CAFs) are the predominant cell type, and the study identifies how the MAPK signaling pathway influences their differentiation into specific phenotypes.
- The study introduces a novel "mapCAF" phenotype associated with certain tumor cells and immune response characteristics, suggesting that targeting these specific CAFs could improve treatment strategies for various cancers.
Background And Aims: Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples.
Methods: In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection.
Glucagon-Producing Pancreatic Neuroendocrine Tumors (Glucagonomas) are Enriched in Aggressive Neoplasms with ARX and PDX1 Co-expression, DAXX/ATRX Mutations, and ALT (Alternative Lengthening of Telomeres).
Endocr Pathol
December 2024
Article Synopsis
- Glucagonomas are special tumors in the pancreas that cause a syndrome and were studied in six patients to understand their features better.
- These tumors were mostly large and showed a common skin symptom called necrolytic migratory erythema in all patients.
- The tumors had specific changes in their genes and were linked to serious aggressive behavior, which means they can spread or grow badly in some patients.
Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.
Int J Cancer
January 2025
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BID variant with an increased risk of developing the disease (OR = 1.
View Article and Find Full Text PDFBackground: Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, underscoring the urgent need for in-depth biological research. The phenomenon of alternative RNA splicing dysregulation is a common hallmark in cancer, including PDAC, presenting new avenues for understanding and developing diagnostic and therapeutic tools. Our research focuses on EIF4A3, a core component of the Exon Junction Complex intimately linked to RNA splicing, and its role in PDAC.
View Article and Find Full Text PDFInactivating alterations in the SWItch/Sucrose NonFermentable (SWI/SNF) Chromatin Remodeling Complex subunits have been described in multiple tumor types. Recent studies focused on SMARC subunits of this complex to understand their relationship with tumor characteristics and therapeutic opportunities. To date, pancreatic cancer with these alterations has not been well studied, although isolated cases of undifferentiated carcinomas have been reported.
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- A study investigates a rare type of cholangiocarcinoma (CCA) with atypical histological features and adenofibromatous lesions, focusing on 8 biliary tumors.
- The tumors exhibited a unique tubulocystic structure reminiscent of certain kidney cancers and were mostly found in older males and females, with a mean size of 4.4 cm and notable histological characteristics, including perineural invasion in one case.
- Genetic analysis revealed shared mutations in chromatin remodeling genes and an actionable fusion gene, leading to the proposal of a new classification termed "tubulocystic carcinoma of bile ducts."
Article Synopsis
- CoRSIVs are regions in the genome with consistent DNA methylation patterns across tissues but show individual differences and are influenced by nearby genetic variants.
- This study focused on investigating SNPs within CoRSIVs and their potential link to pancreatic ductal adenocarcinoma (PDAC) risk, analyzing data from over 14,000 patients and 247,000 controls.
- The research identified that the A allele of SNP rs2976395 is linked to a higher risk of PDAC in Europeans and is associated with changes in DNA methylation and overexpression of the prostate stem cell antigen gene, highlighting the need for further functional studies.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with late diagnoses and ineffective treatments, making surgery the only potential cure for early-stage patients.
- Recent research found that splicing machinery components, particularly PRPF8 and RBMX, are dysregulated in PDAC, correlating with worse patient outcomes and tumor characteristics.
- Modulating these splicing factors in cancer cell lines normalized their expression levels and reduced tumor-related features, suggesting they could be potential targets for new therapies in PDAC.
Article Synopsis
- The study examines the role of SEMA3A, an axon guidance cue, in pancreatic ductal adenocarcinoma (PDAC) progression, highlighting its expression in different PDAC cell types and its impact on cellular behaviors.
- Researchers combined transcriptomic data and experimental approaches to demonstrate that SEMA3A contributes to aggressive cancer traits, including enhanced cell migration and resistance to cell death.
- Findings suggest that SEMA3A promotes a tumor-favorable environment by attracting macrophages and skewing them towards a pro-tumor, M2-like state, while potentially inhibiting effective immune responses from T cells.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression and therapy resistance. To further the understanding of how stiffening of the tumor microenvironment (TME) contributes to aggressiveness, a three-dimensional (3D) self-assembling hydrogel disease model is developed based on peptide amphiphiles (PAs, PA-E3Y) designed to tailor stiffness. The model displays nanofibrous architectures reminiscent of native TME and enables the study of the invasive behavior of PDAC cells.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci.
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- Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that often resists conventional therapies, with over 90% of cases linked to a KRAS mutation, making treatment extremely challenging.
- Researchers studied primary tumor cells from genetically modified mice to understand how PDAC cells develop resistance to MEK inhibitors, analyzing various molecular data to track changes over time.
- They discovered that resistance evolved through the expansion of a single cell clone with significant DNA methylation changes, which were reversible upon drug withdrawal and could be targeted with DNA methyltransferase inhibitors.
Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls.
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- Modern non-Africans have 1-3% Neandertal DNA due to interbreeding events that occurred 50,000-60,000 years ago, which may affect traits linked to diseases like pancreatic ductal adenocarcinoma (PDAC).
- In this study, researchers examined how specific Neandertal-related genetic variations (aSNPs) correlate with PDAC risk in European and East Asian populations, using data from over 200,000 individuals.
- While no significant link was found in Europeans, a specific allele in East Asians was associated with a 35% increased risk of developing PDAC, suggesting only a limited role of Neandertal genes in this cancer's risk.
Signet-ring cell (SRC)/poorly cohesive cell carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its clinicopathologic and molecular profiles based on a multi-institutional cohort of 20 cases. The molecular profiles were investigated using DNA and RNA sequencing.
View Article and Find Full Text PDFIntroduction: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate.
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- Intraductal oncocytic papillary neoplasm (IOPN) is a unique type of pancreatic lesion and a precursor to pancreatic cancer, distinguished from intraductal papillary mucinous neoplasms (IPMNs).
- This study used immunohistochemistry and artificial intelligence to analyze the immune environment in IOPNs, finding that CD8+ T lymphocytes were the most prevalent immune cells, and all tumors showed an activated PD-1/PD-L1 axis.
- The research indicated that while invasive IOPNs had fewer CD4+ cells and larger regions of CD8+ cells, the presence of these immune cells might contribute to the better survival rates observed in IOPN patients.
Long-term organoid culture of a small intestinal neuroendocrine tumor.
Front Endocrinol (Lausanne)
April 2023
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has markedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3 NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly malignant.
View Article and Find Full Text PDFBackground: Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC.
View Article and Find Full Text PDFBackground: The long-term outcomes following surgical resection for pancreatic ductal adenocarcinoma (PDAC) remains poor, with only 20% of patients surviving 5 years after pancreatectomy. Patient selection for surgery remains suboptimal largely due to the absence of consideration of aggressive tumor biology.
Objective: The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes.