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Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response.
Mol Syst Biol
January 2025
Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany.
The DNA-damaging agent Gemcitabine (GEM) is a first-line treatment for pancreatic cancer, but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs, including kinase inhibitors, but the experimental evidence for such rationale is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines.
View Article and Find Full Text PDFTrends in Specific Family Refusals for Pediatric Organ and Tissue Donation: A Cross-Sectional Study.
Pediatr Transplant
February 2025
School of Nursing, University of São Paulo, São Paulo, Brazil.
Background: When a family decides to donate the organs or tissues of their child with brain death, it is necessary to consider which organs or tissues will be donated. This phenomenon presents an ethical dilemma that is underexplored in the scientific literature, making it essential to examine this context to understand how refusals occur within donations.
Objective: To analyze the rates and trends of specific refusals for each organ and tissue from pediatric donors with brain death occurring between 2001 and 2020 in an Organ Procurement Organization in the State of São Paulo, Brazil.
Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.
BMC Cancer
January 2025
Barts Cancer Institute and Wolfson Institute of Public Health, Mary University of London, John Vane Science Centre, Charterhouse Square, London, Queen, EC1M 6BQ, UK.
Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.
View Article and Find Full Text PDFA Phase I, First-In-Human Study of CBA-1205, an Anti-DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors.
Cancer Sci
January 2025
Department of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Japan.
CBA-1205 is a novel humanized antibody targeting delta-like 1 homolog (DLK1) that enhances antibody-dependent cellular cytotoxicity activity. DLK1 overexpression has been reported in various cancer types, such as hepatocellular carcinoma and neuroblastoma. CBA-1205 demonstrates potent antitumor activity in multiple tumor models, making it a potential treatment option for DLK1-expressing cancers.
View Article and Find Full Text PDFGastrointestinal bleeding as debut presentation of solid pseudopapillary pancreatic tumor.
Rev Esp Enferm Dig
January 2025
Aparato Digestivo, Hospital Universitario Torrecárdenas, ESPAÑA.
Solid pseudopapillary pancreatic tumor is a rare entity with low malignant potential and good prognosis that mainly affects young women. The clinical manifestations are nonspecific, most are asymptomatic, and gastrointestinal bleeding, as in the case presented, is rare.
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