A5069230382- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Cancer Research and Treatments
- Ethics in Clinical Research
- Renal cell carcinoma treatment
- Advanced Causal Inference Techniques
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- COVID-19 and healthcare impacts
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Pancreatitis Pathology and Treatment
- Colorectal Cancer Treatments and Studies
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- Lung Cancer Treatments and Mutations
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Cells and Metastasis
- Microbial Natural Products and Biosynthesis
- Proteoglycans and glycosaminoglycans research
Sheba Medical Center
2016-2024
Tel Aviv University
2019-2024
Abstract Pancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation correlated with the dissemination of metastases 1–3 . Here we analysed RNA splicing data a large cohort primary tumours identify differentially spliced events that correlate progression. De novo motif analysis these detected enrichment motifs similarity RBFOX2...
Germline BRCA-associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum response platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable followed by acquired resistance (OS <36 months), (iii) long-term responders >36 months). Patient-derived xenografts (PDX) generated from 25 at different time points. Response...
Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with survival rate of only 12%. Surveillance recommended for high-risk individuals (HRIs), but it not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Cancer Early Detection (PRECEDE) Consortium. Methods: PRECEDE multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18–90 years) are...
Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than 1 year, underscoring the importance evaluating novel targets matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on pro-oncogenic mRNA stability factor HuR (
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinum and PARP inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated heterogeneous responses. Experimental Design: We performed seven-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, which nine were mutated. From 179 whose was whole-genome...
Abstract Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs between May 2020 and March 2022 were collected, with defined as participants PRECEDE meeting guideline-based criteria for PDAC Of 1,273 enrolled, 1,113 eligible inclusion, 47.2% familial...
Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20-30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource peritoneal spread. In study, we utilized ascites/pleural effusion cancer cells establish patient derived xenografts.Ascites/pleural...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA ‐associated PDAC comprises a clinically relevant subtype. A portion these patients are highly susceptible to DNA damaging therapeutics, however, responses heterogeneous and clinical resistance evolves. We have developed unique patient‐derived xenograft (PDX) models from metastatic lesions germline ‐mutated obtained at distinct time points; before treatment progression. Thus, closely mimicking scenarios,...
Modification of acyl carrier proteins (ACP) or domains by the covalent binding a 4'-phosphopantetheine (4'-PP) moiety is fundamental condition for activation fatty acid synthases (FASes) and polyketide (PKSes). Binding 4'-PP mediated 4' phosphopantetheinyl transfersases (PPTases). Mycobacterium tuberculosis (Mtb) possesses two essential PPTases: protein synthase (Mtb AcpS), which activates multidomain I (FAS I), Mtb PptT, an Sfp-type broad spectrum PPTase that PKSes. To date, it has not been...
Syndecan-1 (SDC1) has multiple functions in tumorigenesis general and specifically pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic prognostic biomarker patients with ductal adenocarcinoma (PDAC).In this case-control study, newly diagnosed biopsy-proven PDAC were enrolled alongside healthy individuals derivation-validation cohort design. Serum was measured by enzyme-linked immunoassay. The accuracy of levels for diagnosing computed. A unified enriched additional early-stage used...
Abstract Background Surveillance of high‐risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes PDAC its precursor lesions in BRCA 1/2 pathogenic variants (PVs) carriers undergoing surveillance. Methods A retrospective multicenter cohort surveillance Israeli preferably with a family history PDAC. Results total 180 asymptomatic participated screening programs, including 57 (31.7%) BRCA1 PVs, 121 (67.2%) BRCA2 12...
Abstract Aims and Background Matrix metalloproteinase‐7 (MMP‐7) Syndecan‐1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic prognostic performance of these serum proteins, as potential biomarkers, patients with pancreatic ductal adenocarcinoma (PDAC) benign cysts. Methods In this case–control study, newly diagnosed PDAC ( N = 121) were compared cyst 66) healthy control 48) groups. Serum MMP‐7 SDC1 measured by ELISA. The accuracy their levels...
244 Background: Biliary tract cancers (BTC) exhibit a diverse and high frequency of actionable mutations detectable using next generation sequencing (NGS). The Breast Cancer Linkage Consortium reported that BRCA2 mutation carriers are at increased risk for BTC with estimated relative 4.97, (95% CI = 1. 50-16.52). purpose this study was to evaluate the clinical characteristics germline/somatic BRCA1/2mutations in CCA patients. Methods: Multi-center retrospective analysis patients BRCA1/2-...
<p>Supplementary Figure S1 describes mRNA and protein expression of PARG in shPARG models vitro sensitivity to oxaliplatin.</p>
<p>Supplementary Table 1 describes BRCA and KRAS status of PDX models IC50 PDDX-001 olaparib in PDAC/PDX lines</p>
<p>Supplementary Figure S3 describes synthetic lethality of olaparib with siDDR in PDAC.</p>
<p>Supplementary Fig S2 describes protein expression of PARG across PDAC cell models and drug sensitivity PDAC, KPC, DLD RKO cells to olaparib and/or PDDX-001.</p>
<p>Supplementary Fig S7 describes western blot and RTPCR of PARG in modified shPARG cells.</p>
<p>Supplementary Figure S6 describes cleaved caspase 3 expression and quantitation of H2AX foci in MIA PaCa-2 after combination PDDX-001 oxaliplatin.</p>